MAO-B inhibitors useful for treating obesity

ABSTRACT

The invention provides novel compounds of formulae I and II: 
                         
that are monoamine oxidase-B inhibitors, which can be useful in treating obesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension, dyslipidemias, high blood pressure, and insulin resistance).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the priority benefit of U.S. ProvisionalApplication No. 60/686,585 filed Jun. 2, 2005, now pending, which isincorporated herein by reference.

FIELD OF THE INVENTION

The present invention provides relates to compounds and pharmaceuticalcompositions thereof and methods of using the same for treating obesity.More particularly, the present invention relates to a novel method fortreating obesity using an MAO-B inhibitor.

BACKGROUND OF THE INVENTION

L-Selegiline is a monoamine oxidase (MAO) inhibitor that was developedfor the treatment of neurological disorders and is primarily used totreat Parkinson's disease. MAO is an enzyme responsible for metabolizingbiogenic monoamines including serotonin, dopamine, histamine, andphenylethylamine. By inhibiting MAO located in the central nervoussystem (CNS), MAO inhibitors and their analogues increase theconcentration of monoamines present within the brain synapses. Thisenhances monoamine-mediated neurotransmission, effectively treatingneurological disorders such as Parkinson's disease and depression.

MAO enzymes are also located in a number of peripheral (non-CNS)tissues, including adipocytes, the cells that comprise body fat. Thefunction of MAO enzymes in adipocytes has not been established.Currently, the only approved clinical use of L-selegiline and other MAOinhibitors is for the treatment of neurological disorders such asParkinson's disease and depression.

Obesity is associated with an increase in the overall amount of adiposetissue (i.e., body fat), especially adipose tissue localized in theabdominal area. Obesity has reached epidemic proportions in the UnitedStates. The prevalence of obesity has steadily increased over the yearsamong all racial and ethnic groups. According to the United StatesSurgeon General, 61% of the adult population and 14% of children areobese or overweight. Forty four million Americans are obese, with anadditional eighty million deemed medically overweight. Obesity isresponsible for more than 300,000 deaths annually, and will soonovertake tobacco usage as the primary cause of preventable death in theUnited States. Obesity is a chronic disease that contributes directly tonumerous dangerous co-morbidities, including type 2 diabetes,cardiovascular disease, inflammatory diseases, premature aging, and someforms of cancer. Type 2 diabetes, a serious and life-threateningdisorder with growing prevalence in both adult and childhoodpopulations, is currently the 7^(th) leading cause of death in theUnited States. Since more than 80% of patients with type 2 diabetes areoverweight, obesity is the greatest risk factor for developing type 2diabetes. Increasing clinical evidence indicates that the best way tocontrol type 2 diabetes is to reduce weight.

The most popular over-the counter drugs for the treatment of obesity,phenylpropanolamine and ephedrine, and the most popular prescriptiondrug, fenfluramine, were removed from the marketplace as a result ofsafety concerns. Drugs currently approved for the long-term treatment ofobesity fall into two categories: (a) Central Nervous System (CNS)appetite suppressants such as sibutramine and (b) gut lipase inhibitorssuch as orlistat. CNS appetite suppressants reduce eating behaviorthrough activation of the ‘satiety center’ in the brain and/or byinhibition of the ‘hunger center’ in the brain. Gut lipase inhibitorsreduce the absorption of dietary fat from the gastrointestinal (GI)tract. Although sibutramine and orlistat work through very differentmechanisms, they share in common the same overall goal of reducing bodyweight secondary to reducing the amount of calories that reach thesystemic circulation. Unfortunately, these indirect therapies produceonly a modest initial weight loss (approximately 5% compared toapproximately 2% with placebo) that is usually not maintained. After oneor two years of treatment, most patients return to or exceed theirstarting weight. In addition, most approved anti-obesity therapeuticsproduce undesirable and often dangerous side effects that can complicatetreatment and interfere with a patient's quality of life.

The lack of therapeutic effectiveness, coupled with the spiralingobesity epidemic, positions the ‘treatment of obesity’ as one of thelargest and most urgent unmet medical needs. There is, therefore, a realand continuing need for the development of improved medications thattreat or prevent obesity.

General MAO-B inhibitors such as selegiline have been clinically usefulin the treatment of CNS disorders. They have now unexpectedly beendiscovered to also have anti-obesity activity. Even more surprising isthat the anti-obesity activity mediated by these agents is outside ofthe CNS. This new discovery provides a novel approach for the preventionor treatment of obesity. Moreover, if the CNS effects of these compoundscan be eliminated, their peripherally mediated anti-obesity propertiesshould provide therapeutic agents with greater safety. It has, as aresult, become highly desirable to find MAO-B inhibitors with limited orno CNS effects. Compounds of this sort are expected to be useful intreating obesity and the variety of co-morbidities to which itcontributes.

SUMMARY OF THE INVENTION

Accordingly, in an aspect, the present invention provides novel MAO-Binhibitors or pharmaceutically acceptable salts that are useful to treatobesity, diabetes, and/or cardiometabolic disorders (e.g., hypertension,dyslipidemias, high blood pressure, and insulin resistance).

In another aspect, the present invention provides novel pharmaceuticalcompositions, comprising: a pharmaceutically acceptable carrier and atherapeutically effective amount of at least one of the compounds of thepresent invention or a pharmaceutically acceptable salt form thereof.

In another aspect, the present invention provides novel methods fortreating obesity, diabetes, and/or cardiometabolic disorders (e.g.,hypertension, dyslipidemias, high blood pressure, and insulinresistance), comprising: administering to a patient in need thereof atherapeutically effective amount of at least one of the compounds of thepresent invention or a pharmaceutically acceptable salt form thereof.

In another aspect, the present invention provides novel methods fortreating CNS disorders, comprising: administering to a patient in needthereof a therapeutically effective amount of at least one of thecompounds of the present invention or a pharmaceutically acceptable saltform thereof.

In another aspect, the present invention provides processes forpreparing novel compounds.

In another aspect, the present invention provides novel compounds orpharmaceutically acceptable salts for use in therapy.

In another aspect, the present invention provides the use of novelcompounds for the manufacture of a medicament for the treatment ofobesity, diabetes, and/or cardiometabolic disorders.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat the presently claimed compounds or pharmaceutically acceptable saltforms thereof are expected to be effective MAO-B inhibitors.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is based on the unexpected finding that an MAO-Binhibitor is capable of reducing the amount of adipose tissue (i.e.,body fat) in a warm-blooded mammal. This finding was unexpected becausebody fat can be reduced despite little, if any, concomitant reduction infood intake.

In an embodiment, the present invention provides novel compound A or astereoisomer or a pharmaceutically acceptable salt thereof:

wherein: Q, R, R¹, W, X, X¹, X², and X³ are all independently selectedfrom H and a group capable of reducing or limiting the CNS activity ofcompound A; and,

provided that at least one of Q, R, R¹, W, X, X¹, X², and X³ is otherthan H.

[1] In another embodiment, the present invention provides a novelcompound of formula I or II, or a stereoisomer or pharmaceuticallyacceptable salt thereof:

wherein:

R, at each occurrence, is independently selected from H, C₁₋₆ alkyl,C₂₋₆ alkenyl, and C₂₋₆ alkynyl;

R¹ is selected from H, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,(CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and,(CH₂)_(n)PO(OR)₂;

A⁻ is a counter ion;

V is selected from O⁻, C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl;

X, X¹, X², and X³ are independently selected from H, OR, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, nitro, —CN, N(R)₂,(CH₂)_(m)-tetrazole, (CH₂)_(n)CO₂R, (CH₂)_(n)CONR₂, (CH₂)_(n)CN,O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂,O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃,NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, SO₂NRCH₃,OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl,NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R,O(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)—PO(OR)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₆ alkenyl-CO₂R,O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₆ alkenyl-CO₂R,NR(CH₂)_(n)-aryl-NR(CH₂)_(n) tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-O(CH₂)_(n)tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₆alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN,O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂,O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₆alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole,O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN,O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₆alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₆alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₆alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, NR(CH₂)_(n)heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₆alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)-tetrazole,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, where heteroaryl is a 5-12membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴ and tetrazole is substituted with 0-1 R;

X⁴ is selected from H, OR, O—C₂₋₆ alkenyl, C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl;

Q is selected from H, OH, C₁₋₆ alkoxy, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl, O—C₂₋₆ alkenyl-CO₂R,OCH₂CH₂CONRCH₂CO₂R, OCH₂CHMCONRCH₂CO₂R, O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)SO₂OR, OCH₂CH(NHAc)CO₂R, OCH₂CH(NHR)CO₂R, O(CH₂)_(n)-aryl, andO(CH₂)_(n)-5-12 membered heteroaryl consisting of carbon atoms and from1-4 heteroatoms selected from N, O, and S;

W is selected from H, CO₂R, CON(R)₂, CH₂OH, CH₂OC₁₋₆ alkyl, CH₂OC₂₋₆alkenyl, CH₂O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CON(R)₂, CH₂O—C₂₋₆alkenyl-CO₂R, CH₂OCH₂CH₂CONRCH₂CO₂R, CH₂OCH₂CHMCONRCH₂CO₂R,CH₂O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)SO₂OR, CH₂OCH₂CH(NHAc)CO₂R,CH₂OCH₂CH(NHR)CO₂R, CH₂O—C₂₋₆ alkenyl, and CH₂O(CH₂)_(n)CONH₂,CH₂O(CH₂)_(n)-aryl, and CH₂O(CH₂)_(n)-5-12 membered heteroarylconsisting of carbon atoms and from 1-4 heteroatoms selected from N, O,and S, and wherein heteroaryl is substituted with 1-2 X⁴;

M is independently selected from H, C₁₋₆ alkyl, C₃₋₈ cycloalkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, aryl, (CH₂)_(n)-aryl, heteroaryl, and(CH₂)_(n)-heteroaryl, where heteroaryl is a 5-12 membered ring systemconsisting of carbon atoms and from 1-4 heteroatoms selected from N, O,and S, and wherein aryl and heteroaryl are substituted with 1-2 X⁴;

m is independently selected from 0, 1, 2, 3, and 4; and,

n is independently selected from 1, 2, 3, and 4;

provided that at least one of X, X¹, X², and X³ is other than H, alkyl,alkoxy, hydroxyl, and halo.

In another variant, the compounds of the present invention have no morethan one acid functionality.

[2] In another embodiment, the present invention provides a novelcompound of formula I₁ or II₁, or a stereoisomer or pharmaceuticallyacceptable salt thereof:

[3] In another embodiment, the present invention provides a novelcompound of formula Ia, or a stereoisomer or pharmaceutically acceptablesalt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from H and C₁₋₄ alkyl;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl,O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)heteroaryl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, whereheteroaryl is a 5-10 membered ring system consisting of carbon atoms andfrom 1-4 heteroatoms selected from N, O, and S, and wherein aryl andheteroaryl are substituted with 1-2 X⁴;

X⁴ is selected from H, OH, C₁₋₄ alkoxy, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl;

n is independently selected from 1, 2, and 3;

provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, and halo.

[3a] In another embodiment, the present invention provides a novelcompound of formula Ia, or a stereoisomer or pharmaceutically acceptablesalt thereof, wherein:

one of X and X¹ is H and the other is selected from OH, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C₁₋₄ alkoxy,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl,O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, whereheteroaryl is a 5-10 membered ring system consisting of carbon atoms andfrom 1-4 heteroatoms selected from N, O, and S, and wherein aryl andheteroaryl are substituted with 1-2 X⁴;

provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, and halo.

[4] In another embodiment, the present invention provides a novelcompound of formula Ia₁, or a stereoisomer or pharmaceuticallyacceptable salt thereof:

[5] In another embodiment, the present invention provides a novelcompound of formula Ib, or a stereoisomer or pharmaceutically acceptablesalt thereof:

wherein:

R, at each occurrence, is independently selected from H and C₁₋₄ alkyl;

R¹ is selected from H, C₁₋₄ alkyl, (CH₂)_(m)CO₂R, C₂₋₄ alkenyl-CO₂R,CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, O(CH₂)_(n)CON(R)₂,O—C₂₋₄ alkenyl, N(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl,CH₂-heteroaryl, O(CH₂)_(n)-aryl_(n)O(CH₂ 0 _(n)-heteroaryl,NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, where heteroaryl isa 5-10 membered ring system consisting of carbon atoms and from 1-4heteroatoms selected from N, O, and S, and wherein aryl and heteroarylare substituted with 1-2 X⁴;

X⁴ is selected from H, OH, C₁₋₄ alkoxy, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl;

W is selected from H, CH₂OH, CH₂OC₁₋₄ alkyl, CH₂OC₂₋₄ alkenyl,CH₂O(CH₂)_(n)CO₂R, CH₂O—C₂₋₄ alkenyl-CO₂R, CH₂O(CH₂)_(n)CON(R)₂,CH₂O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)-aryl, and CH₂O(CH₂)_(n)-5-10membered heteroaryl consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S;

m is independently selected from 0, 1, and 2; and,

n is independently selected from 1, 2, and 3;

provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, and halo.

[5a] In another embodiment, the present invention provides a novelcompound of formula Ib, or a stereoisomer or pharmaceutically acceptablesalt thereof, wherein:

one of X and X¹ is H and the other is selected from OH, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C₁₋₄ alkoxy,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl,O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl, NR(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, where heteroaryl isa 5-10 membered ring system consisting of carbon atoms and from 1-4heteroatoms selected from N, O, and S, and wherein aryl and heteroarylare substituted with 1-2 X⁴;

provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, and halo.

[6] In another embodiment, the present invention provides a novelcompound of formula Ib_(l), or a stereoisomer or pharmaceuticallyacceptable salt thereof:

[7] In another embodiment, the present invention provides a novelcompound of formula Ic, or a stereoisomer or pharmaceutically acceptablesalt thereof:

wherein:

R, at each occurrence, is independently selected from H, C₁₋₄ alkyl,C₂₋₄ alkenyl, and C₂₋₄ alkynyl;

R¹ is selected from H and C₁₋₄ alkyl;

X, X¹, X², and X³ are independently selected from H, OR, C₁₋₄ alkyl,C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, N(R)₂,(CH₂)_(m)-tetrazole, (CH₂)_(n)CO₂R, (CH₂)_(n)CONR₂, (CH₂)_(n)CN,O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂,O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃,NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, NR(CH₂)_(n)-tetrazole, SO₂NRCH₃,OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl,NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R,O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(nCON(R)) ₂, O(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR-C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl-O(CH₂)_(n)-tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN,O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂,O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole,O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN,O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)tetrazole, NR(CH₂)_(n)heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)-tetrazole,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, where heteroaryl is a 5-10membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴ and tetrazole is substituted with 0-1 R;

X⁴ is selected from H, OR, C₁₋₄ alkoxy, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl;

A⁻ is selected from Cl and Br;

M is independently selected from H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, aryl, (CH₂)_(n)-aryl, heteroaryl, and(CH₂)_(n)-heteroaryl, where heteroaryl is a 5-12 membered ring systemconsisting of carbon atoms and from 1-4 heteroatoms selected from N, O,and S; and,

m is independently selected from 0, 1, and 2; and,

n is independently selected from 1, 2, and 3;

provided that at least one of X, X¹, X², and X³ is other than H, alkyl,alkoxy, hydroxyl, and halo.

[7a] In another embodiment, the present invention provides a novelcompound of formula Ic, or a stereoisomer or pharmaceutically acceptablesalt thereof, wherein:

three of X, X¹, X², and X³ are H and the fourth is selected from OH,C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, C₁₋₄alkoxy, —CN, N(R)₂, (CH₂)_(m)-tetrazole, (CH₂)_(n)CO₂R, (CH₂)_(n)CONR₂,(CH₂)_(n)CN, O(CH₂)_(n)CN, O(CH₂)_(n)-tetrazole, O(CH₂)_(n)(CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR,NR(CH₂)_(n)-tetrazole, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl,O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(n)CO₂R,O(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)tetrazole,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl, NR(CH₂)_(n)-aryl,NR(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R,O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)-tetrazole, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)—PO(OR)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)—PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)-tetrazole, NR(CH₂)_(m)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)—PO(OR)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)-tetrazole, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl-O(CH₂)_(n)-tetrazole, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-heteroaryl-C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CN,O(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂,O(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-O—C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-heteroarylO(CH₂)_(n)-tetrazole,O(CH₂)_(n)-heteroaryl O(CH₂)_(n)CN,O(CH₂)_(n)-heteroarylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroarylO(CH₂)_(n)—PO(OR)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-heteroaryl-NR—C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-heteroaryl-NR(CH₁)_(n)-tetrazole,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)—PO(OR)₂,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-heteroaryl-C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl(CH₂)_(m)-tetrazole,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CN,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-heteroaryl(CH₂)_(m)—PO(OR)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)-tetrazole, NR(CH₂)_(n)heteroaryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroaryl-NR(CH₂)_(n)PO(OR)₂,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CO₂R, NR(CH₂)_(n)-heteroaryl-O—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)-tetrazole,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CN,NR(CH₂)_(n)-heteroaryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-heteroarylO(CH₂)_(n)PO(OR)₂, where heteroaryl is a 5-10membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴ and tetrazole is substituted with 0-1 R;

provided that at least one of X, X¹, X², and X³ is other than H, alkyl,alkoxy, hydroxyl, and halo.

[8] In another embodiment, the present invention provides a novelcompound of formula Ic₁ or a pharmaceutically acceptable salt thereof:

[9] In another embodiment, the present invention provides a novelcompound of formula Id, or a stereoisomer or pharmaceutically acceptablesalt thereof:

wherein:

R, at each occurrence, is independently selected from H, C₁₋₄ alkyl,C₂₋₄ alkenyl, and C₂₋₄ alkynyl;

R¹ is selected from H, C₁₋₄ alkyl, (CH₂)_(m)CO₂R, (CH₂)_(n)PO(OR)₂, C₂₋₄alkenyl, and C₂₋₄ alkynyl;

X, X¹, and X² are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄alkenyl, N(R)₂, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl,CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂,NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN,NR(CH₂)_(n)-biphenyl-CONH₂, O(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, andNR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂; where heteroaryl is a 5-12membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴;

X⁴ is selected from H, OH, C₁₋₆ alkoxy C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl;

Q is selected from OH, C₁₋₄ alkoxy, O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂,O—C₂₋₄ alkenyl, O—C₂₋₄ alkenyl-CO₂R, OCH₂CH₂CONRCH₂CO₂R,OCH₂CHMCONRCH₂CO₂R, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂CH(NHAc)CO₂R, OCH₂CH(NHR)CO₂R, O(CH₂)_(n)-aryl, and O(CH₂)_(n)-5-10membered heteroaryl consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S;

M is independently selected from H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, aryl, (CH₂)_(n)-aryl, heteroaryl, and(CH₂)_(n)-heteroaryl, where heteroaryl is a 5-12 membered ring systemconsisting of carbon atoms and from 1-4 heteroatoms selected from N, O,and S; and,

m is independently selected from 0, 1, and 2; and,

n is independently selected from 1, 2, and 3;

provided that at least one of X, X¹, and X² is other than H, alkyl,alkoxy, hydroxyl, and halo.

[9a] In another embodiment, the present invention provides a novelcompound of formula Id, or a stereoisomer or pharmaceutically acceptablesalt thereof, wherein:

two of X, X¹, and X² are H and the third is selected from OH, C₁₋₄alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, C₁₋₄ alkoxy,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, N(R)₂, NRSO₂CH₃ , SO₂NRCH₃, CH₂N(C₁₋₄alkyl)₂, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl,O(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)₂CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂,O(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, andNR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂; where heteroaryl is a 5-12membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴;

provided that at least one of X, X¹, and X² is other than H, alkyl,alkoxy, hydroxyl, and halo.

[10] In another embodiment, the present invention provides a novelcompound of formula Id₁, or a stereoisomer or pharmaceuticallyacceptable salt thereof:

[11] In another embodiment, the present invention provides a novelcompound of formula IIa or a stereoisomer thereof:

wherein:

R, at each occurrence, is independently selected from H, C₁₋₄ alkyl,C₂₋₄ alkenyl, and C₂₋₄ alkynyl;

R¹ is selected from H and C₁₋₄ alkyl;

A⁻ is selected from Cl⁻ and Br⁻;

V is selected from O⁻, C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl;

X and X¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, O(CH₂)_(n)CON(R)₂, O—C₂₋₄alkenyl, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl, CH₂-heteroaryl, O(CH₂)_(n)-aryl,O(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂,O(CH₂)_(n)-heteroaryl, O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, andNR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂; where heteroaryl is a 5-12membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴;

X⁴ is selected from H, OR, C₁₋₆ alkoxy C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl;

n is independently selected from 1, 2, and 3;

provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, and halo.

[11a] In another embodiment, the present invention provides a novelcompound of formula IIa or a stereoisomer thereof, wherein:

one of X and X¹ is H and the other is selected from OH, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, C₁₋₄ alkoxy,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl,CH₂-heteroaryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂,NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN,NR(CH₂)_(n)-biphenyl-CONH₂, O(CH₂)_(n)-heteroaryl,O(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂, andNR(CH₂)_(n)-heteroaryl-(CH₂)_(m)CON(R)₂; where heteroaryl is a 5-12membered ring system consisting of carbon atoms and from 1-4 heteroatomsselected from N, O, and S, and wherein aryl and heteroaryl aresubstituted with 1-2 X⁴;

provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, and halo.

[12] In another embodiment, the present invention provides a novelcompound of formula IIa₁:

In another embodiment, the present invention provides novelpharmaceutical compositions, comprising: a pharmaceutically acceptablecarrier and a therapeutically effective amount of a compound of thepresent invention or a stereoisomer or pharmaceutically acceptable saltform thereof.

In another embodiment, the present invention provides a novel method fortreating a disease, comprising: administering to a patient in needthereof a therapeutically effective amount of a compound of the presentinvention or a pharmaceutically acceptable salt form thereof, whereinthe disease is selected from obesity, diabetes, cardiometabolicdisorders, and a combination thereof.

In another embodiment, the cardiometabolic disorder is selected fromhypertension, dyslipidemias (e.g., undesirable blood lipid levels,elevated cholesterol levels, and lowered LDL levels), high bloodpressure, and insulin resistance.

In another embodiment, the present invention provides a novel method fortreating a co-morbidity of obesity, comprising: administering to apatient in need thereof a therapeutically effective amount of a compoundof the present invention or a pharmaceutically acceptable salt formthereof.

In another embodiment, the present invention provides a novel method fortreating a co-morbidity of obesity, comprising: administering to apatient in need thereof a therapeutically effective amount of a compoundof the present invention or a pharmaceutically acceptable salt formthereof.

In another embodiment, the co-morbidity is selected from diabetes,Metabolic Syndrome, dementia, and heart disease.

In another embodiment, the co-morbidity is selected from hypertension;gallbladder disease; gastrointestinal disorders; menstrualirregularities; degenerative arthritis; venous statis ulcers; pulmonaryhypoventilation syndrome; sleep apnea; snoring; coronary artery disease;arterial sclerotic disease; pseudotumor cerebri; accident proneness;increased risks with surgeries; osteoarthritis; high cholesterol; and,increased incidence of malignancies of the ovaries, cervix, uterus,breasts, prostrate, and gallbladder.

In another embodiment, the present invention provides a novel method fortreating a CNS disorder, comprising: administering to a patient in needthereof a therapeutically effective amount of a compound of the presentinvention or a pharmaceutically acceptable salt form thereof.

In another embodiment, the CNS disorder is selected from acute andchronic neurological disorders, cognitive disorders, and memorydeficits. Examples of these disorders include chronic or traumaticdegenerative processes of the nervous system, which include Alzheimer'sdisease, other types of dementia, minimal cognitive impairment, andParkinson's disease. Other examples of CNS disorders include psychiatricdiseases, which include depression, anxiety, panic attack, socialphobia, schizophrenia, and anorexia. Further examples of CNS disordersinclude withdrawal syndromes induced by alcohol, nicotine and otheraddictive drugs. Additional examples of CNS disorders includeneuropathic pain and neuroinflamatory diseases (e.g., multiplesclerosis).

In another embodiment, the present invention also provides a method ofpreventing or reversing the deposition of adipose tissue in a mammal bythe administration of a MAO-B inhibitor. By preventing or reversing thedeposition of adipose tissue, MAO-B inhibitors are expected to reducethe incidence or severity of obesity, thereby reducing the incidence orseverity of associated co-morbidities.

In another embodiment, the present invention provides a compound of thepresent invention for use in therapy.

In another embodiment, the present invention provides the use of thepresent invention for the manufacture of a medicament for the treatmentof obesity, diabetes, cardiometabolic disorders, and a combinationthereof.

The present invention may be embodied in other specific forms withoutdeparting from the spirit or essential attributes thereof. Thisinvention encompasses all combinations of aspects of the invention notedherein. It is understood that any and all embodiments of the presentinvention may be taken in conjunction with any other embodiment orembodiments to describe additional embodiments. It is also to beunderstood that each individual element of the preferred embodiments isintended to be taken individually as its own independent embodiment.Furthermore, any element of an embodiment is meant to be combined withany and all other elements from any embodiment to describe an additionalembodiment.

Definitions

The examples provided in the definitions present in this application arenon-inclusive unless otherwise stated. They include but are not limitedto the recited examples.

The compounds herein described may have asymmetric centers, geometriccenters (e.g., double bond), or both. All chiral, diastereomeric,racemic forms and all geometric isomeric forms of a structure areintended, unless the specific stereochemistry or isomeric form isspecifically indicated. Compounds of the present invention containing anasymmetrically substituted atom may be isolated in optically active orracemic forms. It is well known in the art how to prepare opticallyactive forms, such as by resolution of racemic forms, by synthesis fromoptically active starting materials, or through use of chiralauxiliaries. Geometric isomers of olefins, C═N double bonds, or othertypes of double bonds may be present in the compounds described herein,and all such stable isomers are included in the present invention.Specifically, cis and trans geometric isomers of the compounds of thepresent invention may also exist and may be isolated as a mixture ofisomers or as separated isomeric forms. All processes used to preparecompounds of the present invention and intermediates made therein areconsidered to be part of the present invention. All tautomers of shownor described compounds are also considered to be part of the presentinvention.

“Alkyl” includes both branched and straight-chain saturated aliphatichydrocarbon groups having the specified number of carbon atoms. C₁₋₆alkyl, for example, includes C₁, C₂, C₃, C₄, C₅, and C₆ alkyl groups.Examples of alkyl include methyl, ethyl, n-propyl, i-propyl, n-butyl,s-butyl, t-butyl, n-pentyl, and s-pentyl.

“Alkenyl” includes the specified number of hydrocarbon atoms in eitherstraight or branched configuration with one or more unsaturatedcarbon-carbon bonds that may occur in any stable point along the chain,such as ethenyl and propenyl. C₂₋₆ alkenyl includes C₂, C₃, C₄, C₅, andC₆ alkenyl groups.

“Alkynyl” includes the specified number of hydrocarbon atoms in eitherstraight or branched configuration with one or more triple carbon-carbonbonds that may occur in any stable point along the chain, such asethynyl and propynyl. C₂₋₆ Alkynyl includes C₂, C₃, C₄, C₅, and C₆alkynyl groups.

“Cycloalkyl” includes the specified number of hydrocarbon atoms in asaturated ring, such as cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, and cyclooctyl. C₃₋₈ cycloalkyl includes C₃,C₄, C₅, C₆, C₇, and C₈ cycloalkyl groups.

“Alkoxy” represents an alkyl group as defined above with the indicatednumber of hydrocarbon atoms attached through an oxygen bridge. C₁₋₆alkoxy, includes C₁, C₂, C₃, C₄, C₅, and C₆ alkoxy groups. Examples ofalkoxy include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy,s-butoxy, t-butoxy, n-pentoxy, and s-pentoxy.

“Halo” or “halogen” refers to fluoro, chloro, bromo, and iodo.

“Counterion” is used to represent a small, negatively charged species,such as chloride, bromide, hydroxide, acetate, and sulfate.

“Aryl” refers to any stable 6, 7, 8, 9, 10, 11, 12, or 13 memberedmonocyclic, bicyclic, or tricyclic ring, wherein at least one ring, ifmore than one is present, is aromatic. Examples of aryl includefluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl.

“Heteroaryl” refers to any stable 5, 6, 7, 8, 9, 10, 11, or 12 memberedmonocyclic, bicyclic, or tricyclic heterocyclic ring that is aromatic,and which consists of carbon atoms and 1, 2, 3, or 4 heteroatomsindependently selected from the group consisting of N, O, and S. If theheteroaryl group is bicyclic or tricyclic, then at least one of the twoor three rings must contain a heteroatom, though both or all three mayeach contain one or more heteroatoms. If the heteroaryl group isbicyclic or tricyclic, then only one of the rings must be aromatic. TheN group may be N, NH, or N-substituent, depending on the chosen ring andif substituents are recited. The nitrogen and sulfur heteroatoms mayoptionally be oxidized (e.g., S, S(O), S(O)₂, and N—O). The heteroarylring may be attached to its pendant group at any heteroatom or carbonatom that results in a stable structure. The heteroaryl rings describedherein may be substituted on carbon or on a nitrogen atom if theresulting compound is stable.

Examples of heteroaryl includes acridinyl, azocinyl, benzimidazolyl,benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl,benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl,benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl,4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl,decahydroquinolinyl, 2H,6H-1,5,2-dithiazinyl,dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolyl,1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl,isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl,isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, naphthyridinyl,oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl,1,3,4-oxadiazolyl, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl,phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl,phenoxathinyl, phenoxazinyl, phthalazinyl, pteridinyl, pyranyl,pyrazinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole,pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, 2H-pyrrolyl, pyrrolyl,quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl,tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl,1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4-thiadiazolyl,thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl,thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl,1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl.

Preventing the deposition of adipose tissue covers methods of treatingwherein the levels of adipose tissue of a subject remain about the sameas prior to being treated in accordance with the present invention(i.e., its pre-administration level) or not more than about 1, 2, 3, 4,5, 6, 7, 8, 9, or 10% greater than pre-administration level(particularly when the subject is pre-disposed to increasing adiposetissue levels).

Reversing the deposition of adipose tissue covers methods of treatingwherein the levels of adipose tissue of a subject are lower than thoseprior to being treated in accordance with the present invention (i.e.,its pre-administration level). Examples of lower include 1, 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20% or more lowerthan pre-administration level.

Mammal and patient covers warm blooded mammals that are typically undermedical care (e.g., humans and domesticated animals). Examples ofmammals include (a) feline, canine, equine, bovine, and human and (b)human.

“Treating” or “treatment” covers the treatment of a disease-state in amammal, and includes: (a) inhibiting the disease-state, e.g., arrestingit development; and/or (b) relieving the disease-state, e.g., causingregression of the disease state until a desired endpoint is reached.Treating also includes the amelioration of a symptom of a disease (e.g.,lessen the pain or discomfort), wherein such amelioration may or may notbe directly affecting the disease (e.g., cause, transmission,expression, etc.).

“Pharmaceutically acceptable salts” refer to derivatives of thedisclosed compounds wherein the parent compound is modified by makingacid or base salts thereof. Examples of pharmaceutically acceptablesalts include, but are not limited to, mineral or organic acid salts ofbasic residues such as amines; alkali or organic salts of acidicresidues such as carboxylic acids; and the like. The pharmaceuticallyacceptable salts include the conventional non-toxic salts or thequaternary ammonium salts of the parent compound formed, for example,from non-toxic inorganic or organic acids. For example, suchconventional non-toxic salts include, but are not limited to, thosederived from inorganic and organic acids selected from1,2-ethanedisulfonic, 2-acetoxybenzoic, 2-hydroxyethanesulfonic, acetic,ascorbic, benzenesulfonic, benzoic, bicarbonic, carbonic, citric,edetic, ethane disulfonic, ethane sulfonic, fumaric, glucoheptonic,gluconic, glutamic, glycolic, glycollyarsanilic, hexylresorcinic,hydrabamic, hydrobromic, hydrochloric, hydroiodide, hydroxymaleic,hydroxynaphthoic, isethionic, lactic, lactobionic, lauryl sulfonic,maleic, malic, mandelic, methanesulfonic, napsylic, nitric, oxalic,pamoic, pantothenic, phenylacetic, phosphoric, polygalacturonic,propionic, salicyclic, stearic, subacetic, succinic, sulfamic,sulfanilic, sulfuric, tannic, tartaric, and toluenesulfonic.

The pharmaceutically acceptable salts of the present invention can besynthesized from the parent compound that contains a basic or acidicmoiety by conventional chemical methods. Generally, such salts can beprepared by reacting the free acid or base forms of these compounds witha stoichiometric amount of the appropriate base or acid in water or inan organic solvent, or in a mixture of the two; generally, non-aqueousmedia like ether, ethyl acetate, ethanol, isopropanol, or acetonitrileare preferred. Lists of suitable salts are found in Remington'sPharmaceutical Sciences, 18th ed., Mack Publishing Company, Easton, Pa.,1990, p 1445, the disclosure of which is hereby incorporated byreference.

“Therapeutically effective amount” includes an amount of a compound ofthe present invention that is effective when administered alone or incombination to treat obesity or another indication listed herein.“Therapeutically effective amount” also includes an amount of thecombination of compounds claimed that is effective to treat the desiredindication. The combination of compounds is preferably a synergisticcombination. Synergy, as described, for example, by Chou and Talalay,Adv. Enzyme Regul. 1984, 22:27-55, occurs when the effect of thecompounds when administered in combination is greater than the additiveeffect of the compounds when administered alone as a single agent. Ingeneral, a synergistic effect is most clearly demonstrated atsub-optimal concentrations of the compounds. Synergy can be in terms oflower cytotoxicity, increased effect, or some other beneficial effect ofthe combination compared with the individual components.

Utility

Obesity is defined as having a body mass index (BMI) of 30 or above. Theindex is a measure of an individual's body weight relative to height.BMI is calculated by dividing body weight (in kilograms) by height (inmeters) squared. Normal and healthy body weight is defined as having aBMI between 20 and 24.9. Overweight is defined as having a BMI of 25 orabove. Obesity has reached epidemic proportions in the U.S., with 44million obese Americans, and an additional eighty million deemedmedically overweight.

Obesity is a disease characterized as a condition resulting from theexcess accumulation of adipose tissue, especially adipose tissuelocalized in the abdominal area. It is desirable to treat overweight orobese patients by reducing their amount of adipose tissue, and therebyreducing their overall body weight to within the normal range for theirsex and height. In this way, their risk for co-morbidities such asdiabetes and cardiovascular disease will be reduced. It is alsodesirable to prevent normal weight individuals from accumulatingadditional, excess adipose tissue, effectively maintaining their bodyweights at a BMI<25, and preventing the development of co-morbidities.It is also desirable to control obesity, effectively preventingoverweight and obese individuals from accumulating additional, excessadipose tissue, reducing the risk of further exacerbating theirco-morbidities.

There exist two forms of MAO, designated MAO-A and MAO-B. The two formsdiffer with respect to substrate and inhibitor specificities and aminoacid number and sequence. A preferred substrate for MAO-B isbeta-phenylethylamine. In contrast, a preferred substrate for MAO-A isserotonin. Some MAO inhibitors show selectivity for MAO-A or for MAO-B,whereas other MAO inhibitors show little, if any selectivity. Forexample, the MAO inhibitor clorgyline preferentially inhibits MAO-A; theMAO inhibitor L-selegiline preferentially inhibits MAO-B; and, the MAOinhibitor iproniazid is non-selective (i.e., has a similar affinity forboth). Examples of selectivity include a compound having about 2, 3, 4,5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 100, 200, 300, 400, 500, 600, 700,800, 900, 1000, or more fold higher affinity for one form of MAO thanfor the other form. One of ordinary skill in the art recognizes thatthere can be some difficulty in classifying MAO inhibitors. Somecompounds may selectively inhibit one form of MAO in vitro and then losetheir selectivity in vivo. Also, selectivity of a compound may vary fromspecies to species or from tissue to tissue. In the context of thepresent invention, it is desirable to inhibit MAO-B activity in vivo ina mammal. Thus, selectivity and affinity are based on the in vivoactivity of the MAO inhibitor and the mammalian species to which it isbeing or to be administered. Examples of the selectivity of a MAO-Binhibitor of the present invention include (a) at least a 2, 3, 4, 5, 6,7, 8, 9, 10, 20, 30, 40, 50, to 100-fold greater affinity for MAO-B thanMAO-A in the mammalian species (e.g., human) to be treated and (b) atleast 100-fold greater affinity for MAO-B than MAO-A in the mammalianspecies (e.g., human) to be treated.

Some of the compounds of the present invention have been designed tohave reduced CNS exposure by virtue of their inability or limitedability to penetrate the blood-brain barrier (e.g., quaternary salts oracid substituents) or by their participation in active transportsystems, thus reducing centrally mediated side-effects, a potentialproblem with many anti-obesity agents.

Other compounds of the present invention are expected to penetrate theblood-brain barrier and therefore be useful to treat CNS disorders(e.g., Parkinson's disease, depression, and Alzheimer's disease).

MAO enzymes are also located in a number of peripheral (non-CNS)tissues, including adipocytes; the cells that comprise body fat. Inorder to treat non-CNS disorders (e.g., obesity, diabetes, and/orcardiometabolic disorders), it is necessary to administer enough of adrug sufficient to inhibit MAO in peripheral tissues. MAO inhibitors inuse today to treat various psychiatric and neurological diseases,regardless of route of administration, enter the CNS from the systemiccirculation. While present in the systemic circulation, such drugs haveaccess to peripheral tissues, including adipose tissue, liver, andmuscle. One of skill in the art recognizes that MAO inhibitors intendedto enter the CNS from the systemic circulation in order to treatpsychiatric and neurological diseases also have access to MAO inperipheral tissues, including adipose tissue, liver, and muscle. Thus,an MAO inhibitor useful for treating non-CNS disorders may have someaccess to the CNS from the systemic circulation.

Drugs enter the CNS from the systemic circulation by crossing theblood-brain barrier (BBB). The BBB is a highly specialized ‘gate-keeper’that protects the brain by preventing the entry of many potentiallyharmful substances into the CNS from the systemic circulation. Much isknown about the BBB, and of the physical-chemical properties requiredfor compounds transported across it.

Drugs that do not cross the BBB into the CNS or that are readilyeliminated through transport mechanisms (J Clin Invest. 97, 2517(1996))are known in the literature and have low CNS activity due to theirinability to develop brain levels necessary for pharmacological action.The BBB has at least one mechanism to remove drugs prior to theiraccumulation in the CNS. P-Glycoproteins (P-gp) localized in plasmamembrane of the BBB can influence the brain penetration andpharmacological activity of many drugs through translocation acrossmembranes. The lack of accumulation into the brain by some drugs can beexplained by their active removal from the brain by P-gp residing in theBBB. For example, the typical opioid drug loperamide, clinically used asan antidiarrheal, is actively removed from the brain by P-gp, thusexplaining its lack of opiate-like CNS effects. Another example isdomperidone, a dopamine receptor blocker that participates in the P-gptransport (J Clin Invest. 97, 2517(1996)). Whereas dopamine receptorblockers that cross the BBB can be used to treat schizophrenia, thereadily-eliminated domperidone can be used to prevent emesis, withoutthe likelihood of producing adverse CNS effects.

In addition to the above compounds, agents possessing structuralcharacteristics that retard or prevent BBB penetration or contribute toparticipation in active elimination processes have been identified invarious classes of therapeutics. These include antihistamines (DrugMetab. Dispos. 31, 312 (2003)), beta-adrenergic receptor antagonists(B-blockers)(Eur. J. Clin. Pharmacol. 28, Suppl: 21-3 (1985); Br. J.Clin. Pharmacol., 11 (6), 549-553 (1981)), non-nucleoside reversetranscriptase inhibitors (NNRTIs)(J. Pharm Sci., 88(10) 950-954 (1999)),and opioid antagonists. This latter group has been tested in relation totheir activity in the GI tract. These peripherally selective opioidantagonists are described in various US patents as being useful in thetreatment of non-CNS pathologies in mammals, in particular those of theGI tract (see U.S. Pat. Nos. 5,260,542; 5,434,171; 5,159,081; and5,270,238).

Other types of non-brain penetrant compounds can be prepared through thecreation of a charge within the molecule. Thus, the addition of a methylgroup to the tertiary amine functionality of the drugs scopolamine oratropine, unlike the parent molecules, prevents their passage across theBBB through the presence of a positive charge. However, the newmolecules (methyl-scopolamine and methyl-atropine) retain their fullanticholinergic pharmacological properties. As such, these drugs canalso be used to treat peripheral diseases, without the concern ofadverse CNS effects. The quaternary ammonium compound methylnaltrexoneis also used for the prevention and/or treatment of opioid andnon-opioid induced side effects associated with opioid administration.

MAO-B inhibitors such as selegiline have been useful in the treatment ofCNS disorders. The unexpected discovery that the anti-obesity activitymediated by these agents is mediated by a non-CNS mechanism may make itdesirable that the compounds of the present invention be peripherallyrestricted, i.e., have an inability or limited ability to cross the BBBor be readily eliminated from the brain through active transportsystems, when a non-CNS disorder is to be treated. It may be desirablefor the compounds of the present invention to be peripherallyrestricted, which in turn will result in no or very limited CNS effects.Compounds that provide peripherally mediated anti-obesity propertiesshould result in therapeutic agents with greater safety, as previouslydemonstrated in earlier classes of peripherally restricted agents. Itcan be desirable that the compounds of the present invention, whenadministered in a therapeutically effective amount, have no or verylimited CNS effects. It can also be desirable that the lack of CNSeffects is a result of the compounds of the present invention havingminimal brain concentrations when administered in therapeuticallyeffective amounts. In this context, minimal brain concentrations meanslevels that are too low to be therapeutically effective for thetreatment of a CNS indication or too low to cause significant ormeasurable deleterious or undesired side effects. It is noted that CNSactivity is desirable when seeking to treat a CNS disorder.

Compound A is Rasagiline when Q, R, R¹, W, X, X¹, X², and X³ are all H.Rasagiline is a drug that crosses the BBB and is indicated forParkinson's disease. In compound A, one of R, R¹, R², X, X¹, Y, and Z isa group capable of reducing or limiting the CNS activity of compound A.This reducing or limiting occurs via at least one of R, R¹, R², X, X¹,Y, and Z being a group the either limits compound A's ability to crossthe BBB relative to that of Rasagiline or enables it to be activelyremoved at a level that is higher than Rasagiline's. Examples of brainlevels of compound A include levels that are (a) from 50, 55, 60, 65,70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, to 100% lowerthan Rasagiline, when administered at the same dosage; (b) from 90, 91,92, 93, 94, 95, 96, 97, 98, 99, to 100% lower than Rasagiline, whenadministered at the same dosage; and, (c) from 98, 99, to 100% lowerthan Rasagiline, when administered at the same dosage.

Most methods of treating obesity are dependent on a significantreduction in energy intake, either by a decrease in food intake (e.g.,sibutramine) or by inhibition of fat absorption (e.g., orlistat). In thepresent invention, it can be desirable for adipose tissue to besignificantly reduced in the absence of a significant reduction in foodintake. The weight loss, as a result of the present invention, comesfrom the treatment with an MAO-B inhibitor, largely independent ofappetite and food intake. Examples of the level of food intake duringadipose tissue loss include (a) food intake is maintained, increased orabout 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18,19, or 20% below the normal range of the subject prior to being treatedin accordance with the present invention (i.e., its pre-administrationlevel); (b) food intake is maintained, increased, or about 0, 1, 2, 3,4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% below itspre-administration level; (c) food intake is maintained, increased orabout 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% below its pre-administrationlevel; and (d) food intake level is maintained, increased or about 0, 1,2, 3, 4, or 5% below its pre-administration level.

In some cases, loss of adipose tissue can be accompanied by aconcomitant loss of lean muscle mass. This is particularly evident incancer patients who show a wasting of all body tissue components,including adipose tissue and lean muscle mass. In the present invention,however, it can be desirable for body fat to be significantly reduced inthe absence of a significant reduction in lean body mass. Adipose tissueloss comes from treatment with an MAO-B inhibitor, independent of asignificant change in lean body mass. Examples of the level of lean bodymass during adipose tissue loss include (a) lean body mass ismaintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, or 30% below the normal range of the subject prior to beingtreated in accordance with the present invention (i.e., itspre-administration level); (b) lean body mass is maintained, increased,or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,or 15% below pre-administration levels; (c) lean body mass ismaintained, increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8,9, or 10% below pre-administration levels; and (d) lean body mass ismaintained, increased, or is no more than about 1, 2, 3, 4, or 5% belowpre-administration levels.

In some cases, loss of adipose tissue can be accompanied by aconcomitant loss of water mass. This is particularly evident with dietregimens that promote dehydration. In the present invention, it can bedesirable for body fat to be significantly reduced in the absence of asignificant reduction in water mass. In other words, adipose tissue losscomes from treatment with an MAO-B inhibitor, independent of asignificant change in water mass. Examples of the level of water massduring adipose tissue loss include (a) water mass is maintained,increased, or is no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11,12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29,or 30% below the normal range of the subject prior to being treated inaccordance with the present invention (i.e., its pre-administrationlevel); (b) water mass is maintained, increased, or is no more thanabout 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15% belowpre-administration levels; (c) water mass is maintained, increased, oris no more than about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10% belowpre-administration levels; and (d) water mass is maintained, increased,or is no more than about 1, 2, 3, 4, or 5% below pre-administrationlevels.

Sibutramine and orlistat are currently marketed for use in the treatmentof obesity. These two compounds achieve weight loss through entirelydifferent mechanisms. Sibutramine, a CNS appetite suppressant, inhibitsthe neuronal reuptake of serotonin and noradrenaline. Orlistat inhibitsgut lipase enzymes that are responsible for breaking down ingested fat.

The mechanism of action of MAO-B inhibitors is believed to be entirelydifferent from appetite suppressants, gut lipase inhibitors, and otheragents with similar indications (e.g., serotonin agonists, leptin, fattyacid synthase inhibitors, monoamine oxidase (MAO) inhibitors).Co-administration of a MAO-B inhibitor together with one or more otheragents that are useful for treating the indications described above(e.g., obesity, diabetes, cardiometabolic disorders, and a combinationthereof) is expected to be beneficial, by producing, for example, eitheradditive or synergistic effects. Examples of additional agents includean appetite suppressant and a lipase inhibitor. Therefore, the presentinvention provides a method of treating obesity, diabetes, and/orcardiometabolic disorders, comprising administering a therapeuticallyeffective amount of a compound of the present invention and a secondcomponent selected from an appetite suppressant (e.g., sibutramine,phentermine, fenfluramine) and a gut lipase inhibitor (e.g., orlistat).

MAO-B inhibitors are expected to promote weight loss without appreciablyreducing caloric intake. Co-administration of an MAO-B inhibitortogether with an appetite suppressant is expected to produce eitheradditive or synergistic effects on weight loss. Similarly,co-administration of an MAO-B inhibitor together with a lipase inhibitoris expected to produce either additive or synergistic effects on weightloss.

The ability of compounds to inhibit MAOs can be determined using themethod of R. Uebelhack et al., Pharmacopsychiatry 31, 1988, p187-192 (asdescribed below).

Preparation of platelet-rich plasma and platelets. Venous blood fromhealthy subjects was collected between 8 and 8.30 a.m. after anovernight fast into EDTA-containing vacutainer tubes (11.6 mg EDTA/mlblood). After centrifugation of the blood at 250×g for 15 minutes at 20°C., the supernatant platelet-rich plasma (PRP) was collected and thenumber of platelets in PRP counted with a cell counter (MOIAB, Hilden,Germany). 2 ml of PRP was spun at 1500×g for 10 min to yield a plateletpellet. The pellet was washed three times with ice-cold saline,resuspended in 2 ml Soerensen phoshate buffer, pH 7.4 and stored at −18°C. for one day.

MAO assay. Fresh PRP or frozen platelet suspension (100 μL) wasgenerally preincubated for 10 min in the absence or presence of drugs at37° C. in 100 uL of 0.9% NaCl solution or phosphate buffer pH 7.4,respectively, at 37° C. 50 μL of2-phenylethylamine-[ethyl-1-14C]hydrochloride (P EA) solution (specificactivity 56 Ci/mol, Amersham) was then added in a final concentration of5 μM, and the incubation was continued for 30 min. The reaction wasterminated by the addition of 50 μL of 4M HClO₄. The reaction product ofMAO, phenylacetaldehyde, was extracted into 2 mL of n-hexane. An aliquotof the organic phase was added to scintillator cocktail and theradioactivity was determined using a liquid scintillation counter.Product formation was linear with time for at least 60 min withappropriate platelet numbers. Blank values were obtained by including2mM pargyline in the incubation mixtures. All assays were performed induplicate.

The ability of compounds to inhibit MAO activity can also be determinedusing the following method. cDNA's encoding human MAO-B can betransiently transfected into EBNA cells using the procedure described byE.-J. Schlaeger and K. Christensen (Transient Gene Expression inMammalian Cells Grown in Serum-free Suspension Culture; Cytotechnology,15: 1-13, 1998). After transfection, cells are homogeneized by means ofa Polytron homogeneiser in 20 mM Tris HCl buffer, pH 8.0, containing 0.5mM EGTA and 0.5 mM phenylmethanesulfonyl fluoride. Cell membranes areobtained by centrifugation at 45,000×g and, after two rinsing steps with20 mM Tris HCl buffer, pH 8.0, containing 0.5 mM EGTA, membranes areeventually re-suspended in buffer and aliquots stored at −80° C. untiluse.

MAO-B enzymatic activity can be assayed using a spectrophotometric assayadapted from the method described by M. Zhou and N. Panchuk-Voloshina (AOne-Step Fluorometric Method for the Continuous Measurement of MonoamineOxidase Activity, Analytical Biochemistry, 253: 169-174, 1997). Briefly,membrane aliquots are incubated in 0.1 M potassium phosphate buffer, pH7.4, for 30 min at 37° C. with or without various concentrations of thecompounds. After incubation, the enzymatic reaction is started by theaddition of the MAO substrate tyramine together with 1 U/ml horse-radishperoxidase (Roche Biochemicals) and 80 μMN-acetyl-3,7,-dihydroxyphenoxazine (Amplex Red, Molecular Probes). Thesamples are further incubated for 30 min at 37° C. in a final volume of200 μl and absorbance is determined at a wavelength of 570 nm using aSpectraMax plate reader (Molecular Devices). Background (non-specific)absorbance is determined in the presence of 10 μM L-deprenyl for MAO-B.IC₅₀ values are determined from inhibition curves obtained using nineinhibitor concentrations in duplicate, by fitting data to a fourparameter logistic equation.

Compounds of the present invention are expected to be MAO-B inhibitors.Representative compounds have been tested, as measured in the assaydescribed herein, and have been shown to be active as their IC₅₀ valueswere found to be in the range of ≦10 μM. Compounds of the presentinvention are considered to be MAO-B inhibitors if they have an IC₅₀value less than or equal to 10 μM. Additional examples of desirableactivity levels of MAO-B inhibitors useful in the present inventioninclude (a) an IC₅₀ value of 1 μM or lower, (b) an IC₅₀ value of 0.1 μMor lower, (c) an IC₅₀ value of 0.01 μM or lower, (d) an IC₅₀ value of0.001 μM or lower, and (e) an IC₅₀ value of 0.0001 μM or lower.

In the present invention, MAO-B inhibitor(s) can be administeredenterally, parenterally, orally, and transdermally. One skilled in thisart is aware that the routes of administering the compounds of thepresent invention may vary significantly. In addition to other oraladministrations, sustained release compositions may be favored. Otherexamples of routes include injections (e.g., intravenous, intramuscular,and intraperitoneal); subcutaneous; subdermal implants; buccal,sublingual, topical, rectal, vaginal, and intranasal administrations.Bioerodible, non-bioerodible, biodegradable, and non-biodegradablesystems of administration may also be used.

If a solid composition in the form of tablets is prepared, the mainactive ingredient can be mixed with a pharmaceutical vehicle, examplesof which include silica, starch, lactose, magnesium stearate, and talc.The tablets can be coated with sucrose or another appropriate substanceor they can be treated so as to have a sustained or delayed activity andso as to release a predetermined amount of active ingredientcontinuously. Gelatin capsules can be obtained by mixing the activeingredient with a diluent and incorporating the resulting mixture intosoft or hard gelatin capsules. A syrup or elixir can contain the activeingredient in conjunction with a sweetener, which is preferablycalorie-free, an antiseptic (e.g., methylparaben and/or propylparaben),a flavoring, and an appropriate color. Water-dispersible powders orgranules can contain the active ingredient mixed with dispersants orwetting agents or with suspending agents such as polyvinylpyrrolidone,as well as with sweeteners or taste correctors. Rectal administrationcan be effected using suppositories, which are prepared with bindersmelting at the rectal temperature (e.g., cocoa butter and/orpolyethylene glycols). Parenteral administration can be effected usingaqueous suspensions, isotonic saline solutions, or injectable sterilesolutions, which contain pharmacologically compatible dispersants and/orwetting agents (e.g., propylene glycol and/or polyethylene glycol). Theactive ingredient can also be formulated as microcapsules ormicrospheres, optionally with one or more carriers or additives. Theactive ingredient can also be presented in the form of a complex with acyclodextrin, for example α-, β-, or γ-cyclodextrin,2-hydroxypropyl-β-cyclodextrin, and/or methyl-β-cyclodextrin.

The dose of the MAO-B inhibitor administered daily will vary on anindividual basis and to some extent may be determined by the severity ofthe disease being treated (e.g., obesity). The dose of the MAO-Binhibitor will also vary depending on the MAO-B inhibitor administered.A example of a range of dosages of an MAO-B inhibitor is about from0.001, 0.002, 0.003, 0.004, 0.005, 0.006, 0.007, 0.008, 0.009, 0.01,0.02, 0.03, 0.04, 0.05, 0.06, 0.07, 0.08, 0.09, 0.1, 0.2, 0.3, 0.4, 0.5,0.6, 0.7, 0.8, 0.9, 1.0, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35,40, 45, 50, 55, 60, 65, 70, 76, 80, 85, 90, 95, to 100 mg/kg of mammalbody weight. The MAO-B inhibitor can be administered in a single dose orin a number of smaller doses over a period of time. The length of timeduring which the MAO-B inhibitor is administered varies on an individualbasis, and can continue until the desired results are achieved (i.e.,reduction of body fat, or prevention of a gain in body fat). Therapycould, therefore, last from 1 day to weeks, months, or even yearsdepending upon the subject being treated, the desired results, and howquickly the subject responds to treatment in accordance with the presentinvention.

A possible example of a tablet of the present invention is as follows.

Ingredient mg/Tablet Active ingredient 100 Powdered lactose 95 Whitecorn starch 35 Polyvinylpyrrolidone 8 Na carboxymethylstarch 10Magnesium stearate 2 Tablet weight 250

A possible example of a capsule of the present invention is as follows.

Ingredient mg/Tablet Active ingredient 50 Crystalline lactose 60Microcrystalline cellulose 34 Talc 5 Magnesium stearate 1 Capsule fillweight 150

In the above capsule, the active ingredient has a suitable particlesize. The crystalline lactose and the microcrystalline cellulose arehomogeneously mixed with one another, sieved, and thereafter the talcand magnesium stearate are admixed. The final mixture is filled intohard gelatin capsules of suitable size.

A possible example of an injection solution of the present invention isas follows.

Ingredient mg/Tablet Active substance 1.0 mg 1 N HCl 20.0 μl acetic acid0.5 mg NaCl 8.0 mg Phenol 10.0 mg 1 N NaOH q.s. ad pH 5 H₂O q.s. ad 1 mL

Synthesis

The compounds of the present invention can be prepared in a number ofways known to one skilled in the art of organic synthesis. The compoundsof the present invention can be synthesized using the methods describedbelow, together with synthetic methods known in the art of syntheticorganic chemistry, or by variations thereon as appreciated by thoseskilled in the art. Preferred methods include, but are not limited to,those described below. The reactions are performed in a solventappropriate to the reagents and materials employed and suitable for thetransformations being effected. It will be understood by those skilledin the art of organic synthesis that the functionality present on themolecule should be consistent with the transformations proposed. Thiswill sometimes require a judgment to modify the order of the syntheticsteps or to select one particular process scheme over another in orderto obtain a desired compound of the invention. It will also berecognized that another major consideration in the planning of anysynthetic route in this field is the judicious choice of the protectinggroup used for protection of the reactive functional groups present inthe compounds described in this invention. An authoritative accountdescribing the many alternatives to the trained practitioner is Greeneand Wuts (Protective Groups In Organic Synthesis, Wiley and Sons, 1991).All references cited herein are hereby incorporated in their entiretyherein by reference.

In Scheme 1, the keto acid can be esterified using methanol and sulfuricacid (step a), and subsequent treatment with propargylamine and sodiumcyanoborohydride in slightly acidic media should provide thepropargylamino ester (step b). The corresponding acid can be produced bytreatment with lithium hydroxide in aqueous solution containing aco-solvent (step c). Alternatively, the amino ester can be furtheralkylated with methyl bromide to give the tertary-amino ester (step d),and subsequent lithium hydroxide treatment should give tertiary aminoacid (step e).

As shown in Scheme 2, hydroxyindanone can be benzylated using oneequivalent of sodium hydride and benzyl bromide at low temperature in asolvent such as DMF or THF to give the benzyloxyindanone (step a).Treatment of the ketone with propargylamine and sodium cyanoborohydridein the presence of acetic acid in dichloroethane should provide thesecondary amine (step b). Protection of the secondary amine with tritylchloride in pyridine solution should give the tritylated secondary amine(step c). Deprotonation of the protected propargylamine using n-butyllithium followed by treatment with ethyl bromoacetate should produce theester (step d). Treatment with dry hydrogen bromide in acetic acidshould cause a loss of the trityl protecting group to give benzyloxyaminoester (step e), and subsequent exposure to trifluoroacetic acidshould provide hydroxyindanylamino ester (step f). Lithium hydroxidetreatment should give the secondary amino acid (step g). Alternatively,the benzyloxy-indane amino ester of step e can also be hydrolyzed, asabove, to give the benzyloxy-indane amino acid which may optionally havehalogen, CF₃, alkyl or alkoxy substituents on the phenyl ring.

As shown in Scheme 2′, hydroxyindanone can be benzylated with a varietyof benzyl bromides that are optionally substituted with various groups(e.g., ester, alkylester, oxyalkylester nitrile, alkylnitrile,oxyalkylnitrile, halogen, CF₃, etc.) in acetone at about 60° C. in thepresence of potassium carbonate to give the substitutedbenzyloxyindanones (step a). In the case of substituents on the phenylgroup that are nitriles, treatment of these ketones with propargylamineand sodium cyanoborohydride in acetonitrile and acetic acid at about 30°C. should provide the secondary amine (step b). Hydration of thesenitriles using 30% hydrogen peroxide in DMSO in the presence ofpotassium carbonate at about room temperature should yield thecarboxamides (step c). Alternatively, the nitriles can be converted totetrazoles by treatment with sodium azide and trioctyltin chloride inxylenes at reflux, followed by cleavage of the trialkylstannyl adductwith anhydrous HCl in toluene/THF solution (step f). In the case ofindanones having benzyl groups with ester substituents, reductiveamination with propargyl amine in acetonitrile and acetic acid at 30-50°C. can afford the amino esters (step d). Hydrolysis of the esters usinglithium hydroxide in aqueous THF can produce the acids (step e).Halogen, alkyl, alkoxy and CF3-substituted benzyloxy indanes can beproduced from the indanones via reductive amination as described above.

Scheme 3 describes how indanylpropargylamine (rasagiline) can beprotected with trityl chloride to give the tritylated secondary amine(step a). Treatment with n-butyl lithium followed by methylchloroformate should give the trityl-protected amino ester (step b),which can be de-protected with hydrogen bromide in acetic acid (step c).The corresponding acid can be produced by treatment with aqueous lithiumhydroxide solution (step d).

As illustrated in Scheme 4, a keto acid can be esterified using methanoland sulfuric acid (step a), and subsequent treatment with propargylamineand sodium cyanoborohydride in slightly acidic media should provide thepropargylamino ester (step b). The secondary amine can be protected withtrityl chloride or other suitable protecting groups to give theprotected ester (step c). The ester can then be reduced with lithiumaluminum hydride to give the primary alcohol (step d), which upondeprotonation with sodium hydride and alkylation with ethylbromopropionate should provide the ester (step e). Removal of theprotecting group using hydrogen bromide in acetic acid or other suitabledeprotecting reagents should afford the secondary amino ester (step f),and hydrolysis of the ester with lithium hydroxide in aqueous solutionshould yield the amino acid (step g).

As depicted in Scheme 5, a keto acid can be esterified using methanoland sulfuric acid (step a), and subsequent treatment with propargylamineand sodium cyanoborohydride in slightly acidic media should provide thepropargylamino ester (step b). The secondary amine can be protected withtrityl chloride or other suitable protecting groups to give theprotected ester (step c). The ester can then be reduced with lithiumaluminum hydride to give the primary alcohol (step d) which upondeprotonation with sodium hydride and alkylation with methyl bromideshould provide the ether (step e). Treatment of the methyl ether withn-butyl lithium followed by alkylation with ethyl iodoacetaate shouldprovide the ester (step f). Subsequent deprotection of the amine usinghydrogen bromide in acetic acid or other suitable deprotecting reagents(step g), and subsequent hydrolysis of the ester with lithium hydroxidein aqueous solution will produce the amino acid ether (step h).

Scheme 6 shows alkylation of the hydroxyindanone using potassiumcarbonate in acetone using ethyl bromoacetate at about room temperatureor above can give the indanone ester (step a). Treatment of theketo-ester with propargylamine and sodium cyanoborohydride inacetonitrile in the presence of acetic acid at about 30° C. can providethe secondary amine (step b). Hydrolysis of the ester using lithiumhydroxide in aqueous solution should afford the amino acid (step c).Alternatively, the ester can be alkylated with formalin and sodiumtriacetoxyborohydride in dichloroethane in the presence of acetic acidto give the N-methyl analog which can be hydrolyzed to the acid asdescribed above. Alkylation of the indanone with bromoacetonitrile inacetone in the presence of potassium carbonate at about room temperatureor above can produce the keto-nitrile (step d). Treatment of theketo-nitrile with propargylamine and sodium cyanoborohydride inacetonitrile in the presence of acetic acid at about 30° C. shouldafford the secondary amine (step e). Subsequent hydration of the nitrilewith 30% hydrogen peroxide in DMSO in the presence of potassiumcarbonate can provide the carboxamide (step f).

As shown in Scheme 7, an aminoalcohol can be treated with STABASE(1,1,4,4-tetramethydisilylaza-yclopentane), aryl aldehydes, or othersuitable protecting agents to give a protected amino alcohol (step a).The alcohol can then be deprotonated with sodium hydride and alkylatedwith ethyl bromobutyrate to give the ester (step b). Removal of theprotecting group using tosyl acid in methanol (STABASE) or othersuitable conditions for other protecting groups should afford theprimary amino ester after neutralization (step c). Treatment of thisamine with propioaldehyde diethyl acetal and sodium cyanoborohydrideunder slightly acidic moist conditions should produce the propargylaminoester (step d). Further alkylation of this amine using formalin andsodium cyanoborohydride can provide the methylated teriaryamino ester(step e). Subsequent treatment of the secondary (step f) or the tertiary(step g) amino esters with lithium hydroxide in aqueous solution shouldyield the secondary and tertiary amino acids, respectively.

Scheme 8 shows how tertiary-amino indanes, where Z can be H orO(CH₂)_(n)-phenyl and the phenyl can be optionally substituted withhalogen or CF₃, when treated with an alkyl halides, such as methylbromide or methyl iodide, in a solvent such as toluene, ethanol or ethercan give the corresponding quaternary ammonium salts (step a). Treatmentof these tertiary amines with Davis reagent(phenyloxaziridinebenezene-sulfonamide) in methylene chloride at roomtemperature can give the corresponding amine N-oxides (step b).

One stereoisomer of a compound of the present invention may be a morepotent MAO-B inhibitor than its counterpart(s). Thus, stereoisomers areincluded in the present invention. Some of these stereoisomers are shownbelow in Schemes 9-13. When required, separation of the racemic materialcan be achieved by HPLC using a chiral column or by a resolution using aresolving agent such as described in Wilen, S. H. Tables of ResolvingAgents and Optical Resolutions 1972, 308 or using enantiomerically pureacids and bases. A chiral compound of the present invention may also bedirectly synthesized using a chiral catalyst or a chiral ligand, e.g.,Jacobsen, E. Acc. Chem. Res. 2000, 33, 421-431 or using other enantio-and diastereo-selective reactions and reagents known to one skilled inthe art of asymmetric synthesis.

Other features of the invention will become apparent in the course ofthe following descriptions of exemplary embodiments that are given forillustration of the invention and are not intended to be limitingthereof.

EXAMPLES

Tables A-C below describe examples of the present invention that havebeen synthesized and tested. The activities of the compounds are asfollows:

-   -   +=an IC50 of ≦10 μM;    -   ++=IC50 of ≦1 μM; and,    -   +++=an IC50≦100 nM.

The examples can be prepared according to the methods of the schemenumbers provided for each example.

TABLE A

All compounds racemic Num- Re- Synthesis ber X R sults NMR (CDCl₃-ppm)Route 1 CH₂C₆H₅ H + ring-CH: 1.93 (m) Scheme 2 C≡CH: 2.27 (m) ring-CH:2.41 (m) ring-CH: 2.85 (m) ring-CH: 3.05 (m) N—CH₂: 3.53 (m) N—CH: 4.48(t) PhCH₂O: 5.09 aromatic H's 6.70-7.35 2 CH₂CH₂C₆H₅ H +++ ring-CH: 1.93(m) Scheme 2 C≡CH: 2.26 (m) ring-CH: 2.38 (m) ring-CH: 2.78 (m) ring-CH:2.98 (m) PhOCH₂: 3.09 (t) N—CH₂: 3.51 (q) PhOCH₂: 4.18 (t) N—CH: 4.44(t) aromatic H's 6.78-7.50 3 CH₂CO₂Et CH₃ + ester-CH₃: 1.30 (t) Scheme 6ring-CH₂: 2.17 (m) C≡CH: 2.26 (m) ring-CH: 2.87 (m) ring-CH: 3.00 (m)N—CH₂: 3.35 (dq) ester-CH₂: 4.26 (q) N—CH: 4.52 (t) PhOCH₂: 4.64aromatic H's 6.61-7.26 4 CH₂CO₂Et H + ester-CH₃: 1.29 (t) Scheme 6ring-CH: 1.88 (m) C≡CH: 2.26 (m) ring-CH: 2.41 (m) ring-CH: 2.86 (m)ring-CH: 3.05 (m) N—CH₂: 3.52 (q) ester-CH₂: 4.26 (q) N—CH: 4.43 (t)PhOCH₂: 4.63 aromatic H's 6.61-7.18

TABLE B

All compounds racemic Results NMR (CDCl₃) Synthesis Number X R (B) ppmRoute 5 CH₂C₆H₅ H +++ ring-CH: 2.03 (m) Scheme 2 C≡CH: 2.30 (m) ring-CH:2.39 (m) ring-CH: 2.80 (m) ring-CH: 3.08 (m) N—CH₂: 3.52 (m) N—CH: 4.43(m) PhCH₂O: 5.04 aromatic H's 6.82-7.42 6 CH₂CH₂C₆H₅ H +++ ring-CH: 2.04(m) Scheme 2 C≡CH: 2.32 (m) ring-CH: 2.37 (m) ring-CH: 2.79 (m) ring-CH:3.09 (m) PhCH2: 3.10 (t) N—CH₂: 3.52 (m) N—CH: 4.47 (m) PhOCH₂: 4.15 (t)aromatic H's 6.73-7.26 7 CH₂C₆H₅ CH₃ +++ ring-CH₂: 2.18 (m) Scheme 2C≡CH: 2.30 (m) N—CH₃: 2.38 (s) ring-CH: 2.80 (m) ring-CH: 2.99 (m)N—CH₂: 3.39 (q) N—CH: 4.44 (m) PhCH₂O: 5.05 (s) aromatic H's 6.84-7.50 8CH₂CO₂Et H + (CDCl₃) Scheme 6 ester-CH₃: 1.27 (t) ring-CH: 1.89 (m)C≡CH: 2.25 (m) ring-CH: 2.38 (m) ring-CH: 2.80 (m) ring-CH: 3.00 (m)N—CH₂: 3.49 (m) ester-CH₂: 4.27 (q) N—CH: 4.38 (m) EtO₂CCH₂O: 4.60 (s)aromatic H's 6.73-7.26 9 CH₂CO₂Et CH₃ ++ (CDCl₃) Scheme 6 ester-CH₃:1.29 (t) ring-CH₂: 2.12 (m) C≡CH: 2.24 (m) N—CH₃: 2.32 (s) ring-CH: 2.78(m) ring-CH: 2.95 (m) N—CH₂: 3.32 (q) ester-CH₂: 4.27 (q) N—CH: 4.38 (t)EtO₂CCH₂O: 4.60 (s) aromatic H's 6.76-7.31 10 CH₂CO₂H CH₃ + (CD₃OD)Scheme 6 ring-CH₂: 2.50 (m) N—CH₃: 2.77 (s) ring-CH: 3.00 (m) ring-CH:3.17 (m) C≡CH: 3.38 (m) N—CH₂: 4.05 (dq) HO₂CCH₂O: 4.70 (s) N—CH: 5.09(dd) aromatic H's 6.92-7.51 11 (CH₂)₄CO₂Et H + (CDCl₃) Scheme 6ester-CH₃: 1.26 (t) ring-CH₂: 1.92 (m) C≡CH: 2.27 m) N—CH₃: 2.36 (s)ring-CH: 2.81 (m) ring-CH: 3.05 (m) N—CH₂: 3.50 (s) OCH₂: 3.95 (q)ester-CH₂: 4.13 (q) N—CH: 4.38 (t) aromatic H's 6.72-7.26 12CH₂CH═CHCO₂Et CH₃ +++ (CDCl₃) Scheme 6 ester-CH₃: 1.29 (t) ring-CH₂:2.24 (m) C≡CH: 2.36 m) N—CH₃: 2.44 (s) ring-CH: 2.83 (m) ring-CH: 3.06(m) N—CH₂: 3.46 (br m) ester-CH₂: 4.22 (q) N—CH: 4.52 (m) OCH₂-vinyl:4.69 (q) CH═: 6.19 (2 t) CH═: 7.06 (2 t) aromatic H's 6.78-7.45 13CH₂CH═CHCO₂Et H ++ (CDCl₃) Scheme 6 ester-CH₃: 1.30 (t) ring-CH: 1.93(m) C≡CH: 2.29 (m) ring-CH: 2.40 (m) ring-CH: 2.82 (m) ring-CH: 3.09 (m)N—CH₂: 3.51 (q) ester-CH₂: 4.21 (q) N—CH: 4.41 (t) OCH₂-vinyl: 4.68 (q)CH═: 6.19 (dt) CH═: 7.07 (dt) aromatic H's 6.74-7.3 14 CH₂C₆H₅CO₂Me(4)CH₃ ++ (CDCl₃) Scheme 2′ ring-CH₂: 2.14 (m) C≡CH: 2.25 (m) N—CH₃: 2.33(s) ring-CH 2.78 (m) ring-CH: 2.96 (m) N—CH₂: 3.33 (dq) OCH₃: 3.92 (s)N—CH: 4.39 (t) PhCH₂O: 5.11 (q) aromatic H's 6.8-8.1 15 CH₂C₆H₅CO₂Me(4)H + (CDCl₃) Scheme 2′ ring-CH: 1.94 (m) ring-CH: 2.39 (m) C≡CH: 2.28 (m)ring-CH: 2.80 (m) ring-CH: 3.06 (m) N—CH₂: 3.50 (s) OCH₃: 3.92 (s) N—CH:4.40 (t) PhCH₂O: 5.10 (s) aromatic H's 6.8-8.1 16 CH₂C₆H₅CONH₂(4) H ++(CD₃OD) Scheme 2′ ring-CH: 1.92 (m) ring-CH: 2.35 (m) C≡CH: 2.67 (m)ring-CH: 2.81 (m) ring-CH: 3.02 (m) N—CH₂: 3.46 (q) N—CH: 4.38 (t)PhCH₂O: 5.15 (s) aromatic H's 6.8-7.9 17 CH₂C₆H₅CO₂Me(3) CH₃ ++ (CDCl₃)Scheme 2′ ring-CH₂: 2.14 (m) C≡CH: 2.25 (m) ring-CH: 2.78 (m) ring-CH:2.94 (m) N—CH₂: 3.33 (q) OCH₃: 3.93 (s) N—CH: 4.39 (t) PhCH₂O: 5.09 (s)aromatic H's 6.8-8.15 18 CH₂C₆H₅CO₂Me(3) H +++ (CDCl₃) Scheme 2′ring-CH: 1.89 (m) C≡CH: 2.26 (m) ring-CH: 2.38 (m) ring-CH: 2.80 (m)ring-CH: 3.01 (m) N—CH₂: 3.50 (q) OCH₃: 3.93 (s) N—CH: 4.37 (t) PhCH₂O:5.09 (s) aromatic H's 6.8-8.13 19 CH₂C₆H₅CO₂H(3) H + (CD₃OD) Scheme 2′ring-CH: 2.08 (m) ring-CH: 2.45 (m) ring-CH: 2.90 (m) C≡CH: 2.94 (m)ring-CH: 3.10 (m) N—CH₂: 3.69 (s) N—CH: 4.59 (q) PhCH₂O: 5.14 (s)aromatic H's 6.9-8.10 20 CH₂C₆H₅CONH₂(3) H +++ (CD₃OD) Scheme 2′ring-CH₂: 2.15 (m) C≡CH: 2.69 (m) N—CH₃: 2.33 (s) ring-CH: 2.78 (m)ring-CH: 2.95 (m) N—CH₂: 3.31 (s) OCH₃: 3.92 (s) N—CH: 4.39 (t) PhCH₂O:5.12 (s) aromatic H's 6.85-8.0 21 CH₂C₆H₅CH₂CO₂Me(4) H ++ (CDCl₃) Scheme2′ ring-CH: 1.89 (m) ring-CH: 2.37 (m) ring-CH: 2.79 (m) C≡CH: 2.27 (m)ring-CH: 3.02 (m) N—CH₂: 3.50 (q) PhCH₂CO: 3.65 (s) OCH₃: 3.70 (s) N—CH:4.37 (q) PhCH₂O: 5.13 (s) aromatic H's 6.8-7.45 22 CH₂C₆H₅CH₂CO₂H(4) H~+ (CD₃OD) Scheme 2′ ring-CH: 1.90 (m) ring-CH: 2.37 (m) ring-CH: 2.80(m) C≡CH: 2.27 (m) ring-CH: 3.02 (m) N—CH₂: 3.48 (q) PhCH₂CO: 3.31 (s)N—CH: 4.37 (q) PhCH₂O: 5.03 (s) aromatic H's 6.8-7.35 23CH₂C₆H₅OCH₂CO₂Et(4) H + (CDCl₃) Scheme 2′ ester-CH₃: 1.30 (t) ring-CH:1.89 (m) C≡CH: 2.26 (m) ring-CH: 2.38 (m) ring-CH: 2.78 (m) ring-CH:3.02 (m) N—CH₂: 3.51 (q) ester-CH₂: 4.28 (q) N—CH: 4.37 (t) OCH₂CO: 4.63(s) PhCH₂O: 4.97 (s) aromatic H's 6.80-7.37 24 CH₂C₆H₅OCH₂CONH₂(4) H ++(CD₃OD) Scheme 2′ ring-CH: 1.90 (m) ring-CH: 2.36 (m) C≡CH: 2.68 (m)ring-CH: 2.78 (m) ring-CH: 3.05 (m) N—CH₂: 3.45 (q) OCH₂CO: 4.50 (s)N—CH: 4.37 (q) PhCH₂O: 4.99 (s) aromatic H's 6.8-7.45 25CH₂C₄H₂O—CO₂Me(2,5) H + (CDCl₃) Scheme 2′ (furan) ring-CH: 1.89 (m)C≡CH: 2.26 (m) ring-CH: 2.39 (m) ring-CH: 2.80 (m) ring-CH: 3.00 (m)N—CH₂: 3.50 (q) O—CH₃: 3.90 (s) N—CH: 4.37 (t) OCH₂CO: 4.63 (s)furan-CH₂O: 5.05 (s) furan H's 6.51 (d), 6.80 (d) phenyl H's 6.78-7.2626 CH₂CH₂CH₂PO(OEt)₂ H + (CD₃OD) Scheme 6 ester-CH₃: 1.32 (t) ring-CH:1.98 (m) chain-CH₂'s: 2.00 (m) ring-CH: 2.38 (m) C≡CH: 2.75 (m) ring-CH:2.83 (m) ring-CH: 3.05 (m) N—CH₂: 3.52 (q) ester-CH₂ 4.10 (m) O—CH₂ 4.02(t) N—CH: 4.43 (q) aromatic H's 6.8-7.45

TABLE C

All compounds racemic Synthesis Number X R Results NMR (CDCl₃-ppm) Route27 CH₂C₆H₅ H + ring-CH: 1.90 (m) Scheme 2 C≡CH: 2.24 (m) ring-CH: 2.41(m) ring-CH: 2.76 (m) ring-CH: 2.97 (m) N—CH₂: 3.51 (s) N—CH: 4.40 (m)PhCH₂O: 5.06 aromatic H's 6.85-7.45 28 CH₂C₆H₅ CH₃ + ring-CH₂: 2.13 (m)Scheme 2 C≡CH: 2.26 (m) N—CH₃: 2.34 (s) ring-CH: 2.41 (m) ring-CH: 2.76(m) ring-CH: 2.97 (m) N—CH₂: 3.51 (s) N—CH: 4.46 (m) PhCH₂O: 5.06aromatic H's 6.86-7.50 29 CH₂CH₂C₆H₅ H + ring-CH: 1.92 (m) Scheme 2C≡CH: 2.27 (m) ring-CH: 2.41 (m) ring-CH: 2.75 (m) ring-CH: 3.00 (m)PhOCH₂: 3.10 (t) N—CH₂: 3.52 (q) PhOCH₂: 4.19 (t) N—CH: 4.41 (t)aromatic H's 6.77-7.37 30 CH₂CO₂Et CH₃ + ester-CH₃: 1.30 (t) Scheme 6ring-CH₂: 2.13 (m) C≡CH: 2.26 (m) N—CH₃: 2.32 (s) ring-CH: 2.74 (m)ring-CH: 2.89 (m) N—CH₂: 3.51 (s) ester-CH₂: 4.27 (q) N—CH: 4.43 (m)aromatic H's 6.81-7.28 31 CH₂CH═CHCO₂Et CH₃ ++ ester-CH₃: 1.30 (t)Scheme 6 ring-CH₂: 2.16 (m) C≡CH: 2.29 (m) N—CH₃: 2.37 (s) ring-CH: 2.77(m) ring-CH: 2.90 (m) N—CH₂: 3.37 (m) ester-CH₂: 4.20 (q) N—CH: 4.48 (m)OCH₂-vinyl: 4.70 (m) CH═: 6.19 (dt) CH═: 7.07 (dt) aromatic H's6.80-7.15 32 CH₂CH═CHCO₂Et H + ester-CH₃: 1.30 (t) Scheme 6 ring-CH:1.95 (m) C≡CH: 2.32 (m) ring-CH: 2.44 (m) ring-CH: 2.78 (m) ring-CH:3.00 (m) N—CH₂: 3.54 (m) ester-CH₂: 4.21 (q) N—CH: 4.45 (m) OCH₂-vinyl:4.70 (m) CH═: 6.19 (dt) CH═: 7.07 (dt) aromatic H's 6.80-7.2 33CH₂C₆H₅CO₂Me(4) CH₃ + ring-CH₂: 2.15 (m) Scheme 2′ C≡CH: 2.27 (m) N—CH₃:2.35 (s) ring-CH: 2.75 (m) ring-CH: 2.89 (m) N—CH₂: 3.35 (m) OCH₃: 3.92(s) N—CH: 4.45 (m) PhOCH₂: 5.13 (q) aromatic H's 6.86-8.05 34CH₂C₆H₅CO₂Me(4) H + ring-CH: 1.95 (m) Scheme 2′ C≡CH: 2.26 (m) ring-CH:2.43 (m) ring-CH: 2.77 (m) ring-CH: 2.95 (m) N—CH₂: 3.51 (q) OCH₃: 3.92(s) N—CH: 4.38 (m) PhOCH₂: 5.12 (s) aromatic H's 6.83-8.10 35CH₂C₆H₅CO₂Me(3) H + ring-CH: 1.93 (m) Scheme 2′ C≡CH: 2.29 (m) ring-CH:2.42 (m) ring-CH: 2.77 (m) ring-CH: 2.97 (m) N—CH₂: 3.51 (q) OCH₃: 3.93(s) N—CH: 4.42 (t) PhOCH₂: 5.10 (s) aromatic H's 6.85-8.15 36CH₂C₆H₅OCH₂CN(3) H ++ (CDCl₃) Scheme 2′ ring-CH: 1.87 (m) C≡CH: 2.27 (m)ring-CH: 2.43 (m) ring-CH: 2.77 (m) ring-CH: 2.95 (m) N—CH₂: 3.50 (q)N—CH: 4.37 (t) O—CH₂CN: 4.78 (s) PhCH₂O: 5.06 (s) aromatic H's 6.83-7.3837 CH₂C₆H₅CN(3) H + (CDCl₃) Scheme 2′ ring-CH: 1.87 (m) C≡CH: 2.28 (m)ring-CH: 2.44 (m) ring-CH: 2.78 (m) ring-CH: 2.95 (m) N—CH₂: 3.51 (q)N—CH: 4.38 (t) PhCH₂O: 5.08 (s) aromatic H's 6.82-7.73 38CH₂C₆H₅CONH₂(3) H + (CD₃OD) Scheme 2′ ring-CH: 1.88 (m) ring-CH: 2.37(m) C≡CH: 2.67 (m) ring-CH: 2.75 (m) ring-CH: 2.94 (m) N—CH₂: 3.43 (q)N—CH: 4.38 (t) PhCH₂O: 5.13 (s) aromatic H's 6.86-7.97

Tables I-VI show representative examples of the compounds of the presentinvention. Each example in each table represents an individual speciesof the present invention.

TABLE I

Ex. # X X¹ R R¹ 1 H H CH₃ H 2 H H H H 3 H H CH₃ CH₃ 4 H H H CH₃ 5 OH HCH₃ H 6 OH H H H 7 OH H CH₃ CH₃ 8 OH H H CH₃ 9 H OH CH₃ H 10 H OH H H 11H OH CH₃ CH₃ 12 H OH H CH₃ 13 OCH₃ H CH₃ H 14 OCH₃ H H H 15 OCH₃ H CH₃CH₃ 16 OCH₃ H H CH₃ 17 H OCH₃ CH₃ H 18 H OCH₃ H H 19 H OCH₃ CH₃ CH₃ 20 HOCH₃ H CH₃ 21 OCH₂C₆H₅ H CH₃ H 22 OCH₂C₆H₅ H H H 23 OCH₂C₆H₅ H CH₃ CH₃24 OCH₂C₆H₅ H H CH₃ 25 H OCH₂C₆H₅ CH₃ H 26 H OCH₂C₆H₅ H H 27 H OCH₂C₆H₅CH₃ CH₃ 28 H OCH₂C₆H₅ H CH₃ 29 OCH₂C₆H₅ H CH₃ H 30 OCH₂C₆H₅ H H H 31OCH₂C₆H₅ H CH₃ CH₃ 32 OCH₂C₆H₅ H H CH₃ 33 OCH₂CH₂C₆H₅ H CH₃ H 34OCH₂CH₂C₆H₅ H H H 35 OCH₂CH₂C₆H₅ H CH₃ CH₃ 36 OCH₂CH₂C₆H₅ H H CH₃ 37 HOCH₂CH₂C₆H₅ CH₃ H 38 H OCH₂CH₂C₆H₅ H H 39 H OCH₂CH₂C₆H₅ CH₃ CH₃ 40 HOCH₂CH₂C₆H₅ H CH₃ 41 OCH₂CH═CH₂ H CH₃ H 42 OCH₂CH═CH₂ H H H 43OCH₂CH═CH₂ H CH₃ CH₃ 44 OCH₂CH═CH₂ H H CH₃ 45 H OCH₂CH═CH₂ CH₃ H 46 HOCH₂CH═CH₂ H H 47 H OCH₂CH═CH₂ CH₃ CH₃ 48 H OCH₂CH═CH₂ H CH₃ 49OCH₂CONH₂ H CH₃ H 50 OCH₂CONH₂ H H H 51 OCH₂CONH₂ H CH₃ CH₃ 52 OCH₂CONH₂H H CH₃ 53 H OCH₂CONH₂ CH₃ H 54 H OCH₂CONH₂ H H 55 H OCH₂CONH₂ CH₃ CH₃56 H OCH₂CONH₂ H CH₃ 57 Br H CH₃ H 58 Br H H H 59 Br H CH₃ CH₃ 60 Br H HCH₃ 61 H Cl CH₃ H 62 H Cl H H 63 H Cl CH₃ CH₃ 64 H Cl H CH₃ 65 NO₂ H CH₃H 66 NO₂ H H H 67 NO₂ H CH₃ CH₃ 68 NO₂ H H CH₃ 69 NH₂ H CH₃ H 70 NH₂ H HH 71 NH₂ H CH₃ CH₃ 72 NH₂ H H CH₃ 73 NHSO₂CH₃ H CH₃ H 74 NHSO₂CH₃ H H H75 NHSO₂CH₃ H CH₃ CH₃ 76 NHSO₂CH₃ H H CH₃ 77 H CH₃ CH₃ H 78 H CH₃ H H 79H CH₃ CH₃ CH₃ 80 H CH₃ H CH₃

TABLE IIa

Ex. # X X¹ R¹ 1. H H CO₂CH₂CH₃ 2. H H CO₂H 3. OH H CO₂CH₂CH₃ 4. OH HCO₂H 5. OCH₃ H CO₂CH₂CH₃ 6. OCH₃ H CO₂H 7. OCH₂CH═CH₂ H CO₂CH₂CH₃ 8.OCH₂CH═CH₂ H CO₂H 9. OCH₂C₆H₅ H CO₂CH₂CH₃ 10. OCH₂C₆H₅ H CO₂H 11.OCH₂CH₂C₆H₅ H CO₂CH₂CH₃ 12. OCH₂CH₂C₆H₅ H CO₂H 13. OCH₂CONH₂ H CO₂CH₂CH₃14. OCH₂CONH₂ H CO₂H 15. H Cl CO₂CH₂CH₃ 16. H Cl CO₂H 17. Br H CO₂CH₂CH₃18. Br H CO₂H 19. H CH₃ CO₂CH₂CH₃ 20. H CH₃ CO₂H 21. NO₂ H CO₂CH₂CH₃ 22.NO₂ H CO₂H 23. NH₂ H CO₂CH₂CH₃ 24. NH₂ H CO₂H 25. NHSO₂CH₃ H CO₂CH₂CH₃26. NHSO₂CH₃ H CO₂H 27. H OH CO₂CH₂CH₃ 28. H OH CO₂H 29. H OCH₃CO₂CH₂CH₃ 30. H OCH₃ CO₂H 31. H OCH₂CH═CH₂ CO₂CH₂CH₃ 32. H OCH₂CH═CH₂CO₂H 33. H OCH₂C₆H₅ CO₂CH₂CH₃ 34. H OCH₂C₆H₅ CO₂H 35. H OCH₂CH₂C₆H₅CO₂CH₂CH₃ 36. H OCH₂CH₂C₆H₅ CO₂H 37. H OCH₂CONH₂ CO₂CH₂CH₃ 38. HOCH₂CONH₂ CO₂H 39. H H CH₂CO₂CH₂CH₃ 40. H H CH₂CO₂H 41. OH HCH₂CO₂CH₂CH₃ 42. OH H CH₂CO₂H 43. OCH₃ H CH₂CO₂CH₂CH₃ 44. OCH₃ H CH₂CO₂H45. OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃ 46. OCH₂CH═CH₂ H CH₂CO₂H 47. OCH₂C₆H₅ HCH₂CO₂CH₂CH₃ 48. OCH₂C₆H₅ H CH₂CO₂H 49. OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃ 50.OCH₂CH₂C₆H₅ H CH₂CO₂H 51. OCH₂CONH₂ H CH₂CO₂CH₂CH₃ 52. OCH₂CONH₂ HCH₂CO₂H 53. H Cl CH₂CO₂CH₂CH₃ 54. H Cl CH₂CO₂H 55. Br H CH₂CO₂CH₂CH₃ 56.Br H CH₂CO₂H 57. H CH₃ CH₂CO₂CH₂CH₃ 58. H CH₃ CH₂CO₂H 59. NO₂ HCH₂CO₂CH₂CH₃ 60. NO₂ H CH₂CO₂H 61. NH₂ H CH₂CO₂CH₂CH₃ 62. NH₂ H CH₂CO₂H63. NHSO₂CH₃ H CH₂CO₂CH₂CH₃ 64. NHSO₂CH₃ H CH₂CO₂H 65. H OH CH₂CO₂CH₂CH₃66. H OH CH₂CO₂H 67. H OCH₃ CH₂CO₂CH₂CH₃ 68. H OCH₃ CH₂CO₂H 69. HOCH₂CH═CH₂ CH₂CO₂CH₂CH₃ 70. H OCH₂CH═CH₂ CH₂CO₂H 71. H OCH₂C₆H₅CH₂CO₂CH₂CH₃ 72. H OCH₂C₆H₅ CH₂CO₂H 73. H OCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₃ 74. HOCH₂CH₂C₆H₅ CH₂CO₂H 75. H OCH₂CONH₂ CH₂CO₂CH₂CH₃ 76. H OCH₂CONH₂ CH₂CO₂H77. H H CH₂CH₂CO₂CH₂CH₃ 78. H H CH₂CH₂CO₂H 79. OH H CH₂CO₂CH₂CH₂CH₃ 80.OH H CH₂CH₂CO₂H 81. OCH₃ H CH₂CH₂CO₂CH₂CH₃ 82. OCH₃ H CH₂CH₂CO₂H 83.OCH₂CH═CH₂ H CH₂CO₂CH₂CH₂CH₃ 84. OCH₂CH═CH₂ H CH₂CH₂CO₂H 85. OCH₂C₆H₅ HCH₂CH₂CO₂CH₂CH₃ 86. OCH₂C₆H₅ H CH₂CH₂CO₂H 87. OCH₂CH₂C₆H₅ HCH₂CO₂CH₂CH₂CH₃ 88. OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H 89. OCH₂CONH₂ HCH₂CH₂CO₂CH₂CH₃ 90. OCH₂CONH₂ H CH₂CH₂CO₂H 91. H Cl CH₂CO₂CH₂CH₂CH₃ 92.H Cl CH₂CH₂CO₂H 93. Br H CH₂CH₂CO₂CH₂CH₃ 94. Br H CH₂CH₂CO₂H 95. H CH₃CH₂CO₂CH₂CH₂CH₃ 96. H CH₃ CH₂CH₂CO₂H 97. NO₂ H CH₂CH₂CO₂CH₂CH₃ 98. NO₂ HCH₂CH₂CO₂H 99. NH₂ H CH₂CO₂CH₂CH₂CH₃ 100. NH₂ H CH₂CH₂CO₂H 101. NHSO₂CH₃H CH₂CH₂CO₂CH₂CH₃ 102. NHSO₂CH₃ H CH₂CH₂CO₂H 103. H OH CH₂CO₂CH₂CH₂CH₃104. H OH CH₂CH₂CO₂H 105. H OCH₃ CH₂CH₂CO₂CH₂CH₃ 106. H OCH₃ CH₂CH₂CO₂H107. H OCH₂CH═CH₂ CH₂CO₂CH₂CH₂CH₃ 108. H OCH₂CH═CH₂ CH₂CH₂CO₂H 109. HOCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 110. H OCH₂C₆H₅ CH₂CH₂CO₂H 111. H OCH₂CH₂C₆H₅CH₂CO₂CH₂CH₂CH₃ 112. H OCH₂CH₂C₆H₅ CH₂CH₂CO₂H 113. H OCH₂CONH₂CH₂CH₂CO₂CH₂CH₃ 114. H OCH₂CONH₂ CH₂CH₂CO₂H 115. H H CH₂CH₂PO(OCH₂CH₃)₂116. H H CH₂CH₂PO(OH)₂ 117. OH H CH₂CH₂PO(OCH₂CH₃)₂ 118. OH HCH₂CH₂PO(OH)₂ 119. OCH₃ H CH₂CH₂PO(OCH₂CH₃)₂ 120. OCH₃ H CH₂CH₂PO(OH)₂121. OCH₂CH═CH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 122. OCH₂CH═CH₂ H CH₂CH₂PO(OH)₂123. OCH₂C₆H₅ H CH₂CH₂PO(OCH₂CH₃)₂ 124. OCH₂C₆H₅ H CH₂CH₂PO(OH)₂ 125.OCH₂CH₂C₆H₅ H CH₂CH₂PO(OCH₂CH₃)₂ 126. OCH₂CH₂C₆H₅ H CH₂CH₂PO(OH)₂ 127.OCH₂CONH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 128. OCH₂CONH₂ H CH₂CH₂PO(OH)₂ 129. H ClCH₂CH₂PO(OCH₂CH₃)₂ 130. H Cl CH₂CH₂PO(OH)₂ 131. Br H CH₂CH₂PO(OCH₂CH₃)₂132. Br H CH₂CH₂PO(OH)₂ 133. H CH₃ CH₂CH₂PO(OCH₂CH₃)₂ 134. H CH₃CH₂CH₂PO(OH)₂ 135. NO₂ H CH₂CH₂PO(OCH₂CH₃)₂ 136. NO₂ H CH₂CH₂PO(OH)₂137. NH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 138. NH₂ H CH₂CH₂PO(OH)₂ 139. NHSO₂CH₃ HCH₂CH₂PO(OCH₂CH₃)₂ 140. NHSO₂CH₃ H CH₂CH₂PO(OH)₂ 141. H OHCH₂CH₂PO(OCH₂CH₃)₂ 142. H OH CH₂CH₂PO(OH)₂ 143. H OCH₃CH₂CH₂PO(OCH₂CH₃)₂ 144. H OCH₃ CH₂CH₂PO(OH)₂ 145. H OCH₂CH═CH₂CH₂CH₂PO(OCH₂CH₃)₂ 146. H OCH₂CH═CH₂ CH₂CH₂PO(OH)₂ 147. H OCH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂ 148. H OCH₂C₆H₅ CH₂CH₂PO(OH)₂ 149. H OCH₂CH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂ 150. H OCH₂CH₂C₆H₅ CH₂CH₂PO(OH)₂ 151. H OCH₂CONH₂CH₂CH₂PO(OCH₂CH₃)₂ 152. H OCH₂CONH₂ CH₂CH₂PO(OH)₂ 153. H HCH₂CH═CHCO₂CH₂CH₃ 154. H H CH₂CH═CHCO₂H 155. OH H CH₂CH═CHCO₂CH₂CH₃ 156.OH H CH₂CH═CHCO₂H 157. OCH₃ H CH₂CH═CHCO₂CH₂CH₃ 158. OCH₃ H CH₂CH═CHCO₂H159. OCH₂CH═CH₂ H CH₂CH═CHCO₂CH₂CH₃ 160. OCH₂CH═CH₂ H CH₂CH═CHCO₂H 161.OCH₂C₆H₅ H CH₂CH═CHCO₂CH₂CH₃ 162. OCH₂C₆H₅ H CH₂CH═CHCO₂H 163.OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂CH₂CH₃ 164. OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂H 165.OCH₂CONH₂ H CH₂CH═CHCO₂CH₂CH₃ 166. OCH₂CONH₂ H CH₂CH═CHCO₂H 167. H ClCH₂CH═CHCO₂CH₂CH₃ 168. H Cl CH₂CH═CHCO₂H 169. Br H CH₂CH═CHCO₂CH₂CH₃170. Br H CH₂CH═CHCO₂H 171. H CH₃ CH₂CH═CHCO₂CH₂CH₃ 172. H CH₃CH₂CH═CHCO₂H 173. NO₂ H CH₂CH═CHCO₂CH₂CH₃ 174. NO₂ H CH₂CH═CHCO₂H 175.NH₂ H CH₂CH═CHCO₂CH₂CH₃ 176. NH₂ H CH₂CH═CHCO₂H 177. NHSO₂CH₃ HCH₂CH═CHCO₂CH₂CH₃ 178. NHSO₂CH₃ H CH₂CH═CHCO₂H 179. H OHCH₂CH═CHCO₂CH₂CH₃ 180. H OH CH₂CH═CHCO₂H 181. H OCH₃ CH₂CH═CHCO₂CH₂CH₃182. H OCH₃ CH₂CH═CHCO₂H 183. H OCH₂CH═CH₂ CH₂CH═CHCO₂CH₂CH₃ 184. HOCH₂CH═CH₂ CH₂CH═CHCO₂H 185. H OCH₂C₆H₅ CH₂CH═CHCO₂CH₂CH₃ 186. HOCH₂C₆H₅ CH₂CH═CHCO₂H 187. H OCH₂CH₂C₆H₅ CH₂CH═CHCO₂CH₂CH₃ 188. HOCH₂CH₂C₆H₅ CH₂CH═CHCO₂H 189. H OCH₂CONH₂ CH₂CH═CHCO₂CH₂CH₃ 190. HOCH₂CONH₂ CH₂CH═CHCO₂H

TABLE IIb

Ex. # X X¹ R¹  1. H H CO₂CH₂CH₃  2. H H CO₂H  3. OH H CO₂CH₂CH₃  4. OH HCO₂H  5. OCH₃ H CO₂CH₂CH₃  6. OCH₃ H CO₂H  7. OCH₂CH═CH₂ H CO₂CH₂CH₃  8.OCH₂CH═CH₂ H CO₂H  9. OCH₂C₆H₅ H CO₂CH₂CH₃  10. OCH₂C₆H₅ H CO₂H  11.OCH₂CH₂C₆H₅ H CO₂CH₂CH₃  12. OCH₂CH₂C₆H₅ H CO₂H  13. OCH₂CONH₂ HCO₂CH₂CH₃  14. OCH₂CONH₂ H CO₂H  15. H Cl CO₂CH₂CH₃  16. H Cl CO₂H  17.Br H CO₂CH₂CH₃  18. Br H CO₂H  19. H CH₃ CO₂CH₂CH₃  20. H CH₃ CO₂H  21.NO₂ H CO₂CH₂CH₃  22. NO₂ H CO₂H  23. NH₂ H CO₂CH₂CH₃  24. NH₂ H CO₂H 25. NHSO₂CH₃ H CO₂CH₂CH₃  26. NHSO₂CH₃ H CO₂H  27. H OH CO₂CH₂CH₃  28.H OH CO₂H  29. H OCH₃ CO₂CH₂CH₃  30. H OCH₃ CO₂H  31. H OCH₂CH═CH₂CO₂CH₂CH₃  32. H OCH₂CH═CH₂ CO₂H  33. H OCH₂C₆H₅ CO₂CH₂CH₃  34. HOCH₂C₆H₅ CO₂H  35. H OCH₂CH₂C₆H₅ CO₂CH₂CH₃  36. H OCH₂CH₂C₆H₅ CO₂H  37.H OCH₂CONH₂ CO₂CH₂CH₃  38. H OCH₂CONH₂ CO₂H  39. H H CH₂CO₂CH₂CH₃  40. HH CH₂CO₂H  41. OH H CH₂CO₂CH₂CH₃  42. OH H CH₂CO₂H  43. OCH₃ HCH₂CO₂CH₂CH₃  44. OCH₃ H CH₂CO₂H  45. OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃  46.OCH₂CH═CH₂ H CH₂CO₂H  47. OCH₂C₆H₅ H CH₂CO₂CH₂CH₃  48. OCH₂C₆H₅ HCH₂CO₂H  49. OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃  50. OCH₂CH₂C₆H₅ H CH₂CO₂H  51.OCH₂CONH₂ H CH₂CO₂CH₂CH₃  52. OCH₂CONH₂ H CH₂CO₂H  53. H Cl CH₂CO₂CH₂CH₃ 54. H Cl CH₂CO₂H  55. Br H CH₂CO₂CH₂CH₃  56. Br H CH₂CO₂H  57. H CH₃CH₂CO₂CH₂CH₃  58. H CH₃ CH₂CO₂H  59. NO₂ H CH₂CO₂CH₂CH₃  60. NO₂ HCH₂CO₂H  61. NH₂ H CH₂CO₂CH₂CH₃  62. NH₂ H CH₂CO₂H  63. NHSO₂CH₃ HCH₂CO₂CH₂CH₃  64. NHSO₂CH₃ H CH₂CO₂H  65. H OH CH₂CO₂CH₂CH₃  66. H OHCH₂CO₂H  67. H OCH₃ CH₂CO₂CH₂CH₃  68. H OCH₃ CH₂CO₂H  69. H OCH₂CH═CH₂CH₂CO₂CH₂CH₃  70. H OCH₂CH═CH₂ CH₂CO₂H  71. H OCH₂C₆H₅ CH₂CO₂CH₂CH₃  72.H OCH₂C₆H₅ CH₂CO₂H  73. H OCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₃  74. H OCH₂CH₂C₆H₅CH₂CO₂H  75. H OCH₂CONH₂ CH₂CO₂CH₂CH₃  76. H OCH₂CONH₂ CH₂CO₂H  77. H HCH₂CH₂CO₂CH₂CH₃  78. H H CH₂CH₂CO₂H  79. OH H CH₂CO₂CH₂CH₂CH₃  80. OH HCH₂CH₂CO₂H  81. OCH₃ H CH₂CH₂CO₂CH₂CH₃  82. OCH₃ H CH₂CH₂CO₂H  83.OCH₂CH═CH₂ H CH₂CO₂CH₂CH₂CH₃  84. OCH₂CH═CH₂ H CH₂CH₂CO₂H  85. OCH₂C₆H₅H CH₂CH₂CO₂CH₂CH₃  86. OCH₂C₆H₅ H CH₂CH₂CO₂H  87. OCH₂CH₂C₆H₅ HCH₂CO₂CH₂CH₂CH₃  88. OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H  89. OCH₂CONH₂ HCH₂CH₂CO₂CH₂CH₃  90. OCH₂CONH₂ H CH₂CH₂CO₂H  91. H Cl CH₂CO₂CH₂CH₂CH₃ 92. H Cl CH₂CH₂CO₂H  93. Br H CH₂CH₂CO₂CH₂CH₃  94. Br H CH₂CH₂CO₂H  95.H CH₃ CH₂CO₂CH₂CH₂CH₃  96. H CH₃ CH₂CH₂CO₂H  97. NO₂ H CH₂CH₂CO₂CH₂CH₃ 98. NO₂ H CH₂CH₂CO₂H  99. NH₂ H CH₂CO₂CH₂CH₂CH₃ 100. NH₂ H CH₂CH₂CO₂H101. NHSO₂CH₃ H CH₂CH₂CO₂CH₂CH₃ 102. NHSO₂CH₃ H CH₂CH₂CO₂H 103. H OHCH₂CO₂CH₂CH₂CH₃ 104. H OH CH₂CH₂CO₂H 105. H OCH₃ CH₂CH₂CO₂CH₂CH₃ 106. HOCH₃ CH₂CH₂CO₂H 107. H OCH₂CH═CH₂ CH₂CO₂CH₂CH₂CH₃ 108. H OCH₂CH═CH₂CH₂CH₂CO₂H 109. H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃ 110. H OCH₂C₆H₅ CH₂CH₂CO₂H111. H OCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₂CH₃ 112. H OCH₂CH₂C₆H₅ CH₂CH₂CO₂H 113. HOCH₂CONH₂ CH₂CH₂CO₂CH₂CH₃ 114. H OCH₂CONH₂ CH₂CH₂CO₂H 115. H HCH₂CH₂PO(OCH₂CH₃)₂ 116. H H CH₂CH₂PO(OH)₂ 117. OH H CH₂CH₂PO(OCH₂CH₃)₂118. OH H CH₂CH₂PO(OH)₂ 119. OCH₃ H CH₂CH₂PO(OCH₂CH₃)₂ 120. OCH₃ HCH₂CH₂PO(OH)₂ 121. OCH₂CH═CH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 122. OCH₂CH═CH₂ HCH₂CH₂PO(OH)₂ 123. OCH₂C₆H₅ H CH₂CH₂PO(OCH₂CH₃)₂ 124. OCH₂C₆H₅ HCH₂CH₂PO(OH)₂ 125. OCH₂CH₂C₆H₅ H CH₂CH₂PO(OCH₂CH₃)₂ 126. OCH₂CH₂C₆H₅ HCH₂CH₂PO(OH)₂ 127. OCH₂CONH₂ H CH₂CH₂PO(OCH₂CH₃)₂ 128. OCH₂CONH₂ HCH₂CH₂PO(OH)₂ 129. H Cl CH₂CH₂PO(OCH₂CH₃)₂ 130. H Cl CH₂CH₂PO(OH)₂ 131.Br H CH₂CH₂PO(OCH₂CH₃)₂ 132. Br H CH₂CH₂PO(OH)₂ 133. H CH₃CH₂CH₂PO(OCH₂CH₃)₂ 134. H CH₃ CH₂CH₂PO(OH)₂ 135. NO₂ HCH₂CH₂PO(OCH₂CH₃)₂ 136. NO₂ H CH₂CH₂PO(OH)₂ 137. NH₂ HCH₂CH₂PO(OCH₂CH₃)₂ 138. NH₂ H CH₂CH₂PO(OH)₂ 139. NHSO₂CH₃ HCH₂CH₂PO(OCH₂CH₃)₂ 140. NHSO₂CH₃ H CH₂CH₂PO(OH)₂ 141. H OHCH₂CH₂PO(OCH₂CH₃)₂ 142. H OH CH₂CH₂PO(OH)₂ 143. H OCH₃CH₂CH₂PO(OCH₂CH₃)₂ 144. H OCH₃ CH₂CH₂PO(OH)₂ 145. H OCH₂CH═CH₂CH₂CH₂PO(OCH₂CH₃)₂ 146. H OCH₂CH═CH₂ CH₂CH₂PO(OH)₂ 147. H OCH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂ 148. H OCH₂C₆H₅ CH₂CH₂PO(OH)₂ 149. H OCH₂CH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂ 150. H OCH₂CH₂C₆H₅ CH₂CH₂PO(OH)₂ 151. H OCH₂CONH₂CH₂CH₂PO(OCH₂CH₃)₂ 152. H OCH₂CONH₂ CH₂CH₂PO(OH)₂ 153. H HCH₂CH═CHCO₂CH₂CH₃ 154. H H CH₂CH═CHCO₂H 155. OH H CH₂CH═CHCO₂CH₂CH₃ 156.OH H CH₂CH═CHCO₂H 157. OCH₃ H CH₂CH═CHCO₂CH₂CH₃ 158. OCH₃ H CH₂CH═CHCO₂H159. OCH₂CH═CH₂ H CH₂CH═CHCO₂CH₂CH₃ 160. OCH₂CH═CH₂ H CH₂CH═CHCO₂H 161.OCH₂C₆H₅ H CH₂CH═CHCO₂CH₂CH₃ 162. OCH₂C₆H₅ H CH₂CH═CHCO₂H 163.OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂CH₂CH₃ 164. OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂H 165.OCH₂CONH₂ H CH₂CH═CHCO₂CH₂CH₃ 166. OCH₂CONH₂ H CH₂CH═CHCO₂H 167. H ClCH₂CH═CHCO₂CH₂CH₃ 168. H Cl CH₂CH═CHCO₂H 169. Br H CH₂CH═CHCO₂CH₂CH₃170. Br H CH₂CH═CHCO₂H 171. H CH₃ CH₂CH═CHCO₂CH₂CH₃ 172. H CH₃CH₂CH═CHCO₂H 173. NO₂ H CH₂CH═CHCO₂CH₂CH₃ 174. NO₂ H CH₂CH═CHCO₂H 175.NH₂ H CH₂CH═CHCO₂CH₂CH₃ 176. NH₂ H CH₂CH═CHCO₂H 177. NHSO₂CH₃ HCH₂CH═CHCO₂CH₂CH₃ 178. NHSO₂CH₃ H CH₂CH═CHCO₂H 179. H OHCH₂CH═CHCO₂CH₂CH₃ 180. H OH CH₂CH═CHCO₂H 181. H OCH₃ CH₂CH═CHCO₂CH₂CH₃182. H OCH₃ CH₂CH═CHCO₂H 183. H OCH₂CH═CH₂ CH₂CH═CHCO₂CH₂CH₃ 184. HOCH₂CH═CH₂ CH₂CH═CHCO₂H 185. H OCH₂C₆H₅ CH₂CH═CHCO₂CH₂CH₃ 186. HOCH₂C₆H₅ CH₂CH═CHCO₂H 187. H OCH₂CH₂C₆H₅ CH₂CH═CHCO₂CH₂CH₃ 188. HOCH₂CH₂C₆H₅ CH₂CH═CHCO₂H 189. H OCH₂CONH₂ CH₂CH═CHCO₂CH₂CH₃ 190. HOCH₂CONH₂ CH₂CH═CHCO₂H

TABLE III

Ex. # X X¹ R¹ R”  1. H H H CH₂—CO₂CH₂CH₃  2. H H CH₃ CH₂—CO₂H  3. OH H HCH₂—CO₂CH₂CH₃  4. OH H CH₃ CH₂—CO₂H  5. OCH₃ H H CH₂—CO₂CH₂CH₃  6. OCH₃H CH₃ CH₂—CO₂H  7. OCH₂CH═CH₂ H H CH₂—CO₂CH₂CH₃  8. OCH₂CH═CH₂ H CH₃CH₂—CO₂H  9. OCH₂C₆H₅ H H CH₂—CO₂CH₂CH₃  10. OCH₂C₆H₅ H CH₃ CH₂—CO₂H 11. OCH₂CH₂C₆H₅ H H CH₂—CO₂CH₂CH₃  12. OCH₂CH₂C₆H₅ H CH₃ CH₂—CO₂H  13.OCH₂—CONH₂ H H CH₂—CO₂CH₂CH₃  14. OCH₂—CONH₂ H CH₃ CH₂—CO₂H  15. H Cl HCH₂—CO₂CH₂CH₃  16. H Cl CH₃ CH₂—CO₂H  17. Br H H CH₂—CO₂CH₂CH₃  18. Br HCH₃ CH₂—CO₂H  19. H CH₃ H CH₂—CO₂CH₂CH₃  20. H CH₃ CH₃ CH₂—CO₂H  21. NO₂H H CH₂—CO₂CH₂CH₃  22. NO₂ H CH₃ CH₂—CO₂H  23. NH₂ H H CH₂—CO₂CH₂CH₃ 24. NH₂ H CH₃ CH₂—CO₂H  25. NHSO₂CH₃ H H CH₂—CO₂CH₂CH₃  26. NHSO₂CH₃ HCH₃ CH₂—CO₂H  27. H OH H CH₂—CO₂CH₂CH₃  28. H OH CH₃ CH₂—CO₂H  29. HOCH₃ H CH₂—CO₂CH₂CH₃  30. H OCH₃ CH₃ CH₂—CO₂H  31. H OCH₂CH═CH₂ HCH₂—CO₂CH₂CH₃  32. H OCH₂CH═CH₂ CH₃ CH₂—CO₂H  33. H OCH₂C₆H₅ HCH₂—CO₂CH₂CH₃  34. H OCH₂C₆H₅ CH₃ CH₂—CO₂H  35. H OCH₂CH₂C₆H₅ HCH₂—CO₂CH₂CH₃  36. H OCH₂CH₂C₆H₅ CH₃ CH₂—CO₂H  37. H OCH₂—CONH₂ HCH₂—CO₂CH₂CH₃  38. H OCH₂—CONH₂ CH₃ CH₂—CO₂H  39. H H H CH₂CH₂—CO₂CH₂CH₃ 40. H H CH₃ CH₂CH₂—CO₂H  41. OH H H CH₂CH₂—CO₂CH₂CH₃  42. OH H CH₃CH₂CH₂—CO₂H  43. OCH₃ H H CH₂CH₂—CO₂CH₂CH₃  44. OCH₃ H CH₃ CH₂CH₂—CO₂H 45. OCH₂CH═CH₂ H H CH₂CH₂—CO₂CH₂CH₃  46. OCH₂CH═CH₂ H CH₃ CH₂CH₂—CO₂H 47. OCH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃  48. OCH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H  49.OCH₂CH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃  50. OCH₂CH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H  51.OCH₂—CONH₂ H H CH₂CH₂—CO₂CH₂CH₃  52. OCH₂—CONH₂ H CH₃ CH₂CH₂—CO₂H  53. HCl H CH₂CH₂—CO₂CH₂CH₃  54. H Cl CH₃ CH₂CH₂—CO₂H  55. Br H HCH₂CH₂—CO₂CH₂CH₃  56. Br H CH₃ CH₂CH₂—CO₂H  57. H CH₃ H CH₂CH₂—CO₂CH₂CH₃ 58. H CH₃ CH₃ CH₂CH₂—CO₂H  59. NO₂ H H CH₂CH₂—CO₂CH₂CH₃  60. NO₂ H CH₃CH₂CH₂—CO₂H  61. NH₂ H H CH₂CH₂—CO₂CH₂CH₃  62. NH₂ H CH₃ CH₂CH₂—CO₂H 63. NHSO₂CH₃ H H CH₂CH₂—CO₂CH₂CH₃  64. NHSO₂CH₃ H CH₃ CH₂CH₂—CO₂H  65.H OH H CH₂CH₂—CO₂CH₂CH₃  66. H OH CH₃ CH₂CH₂—CO₂H  67. H OCH₃ HCH₂CH₂—CO₂CH₂CH₃  68. H OCH₃ CH₃ CH₂CH₂—CO₂H  69. H OCH₂CH═CH₂ HCH₂CH₂—CO₂CH₂CH₃  70. H OCH₂CH═CH₂ CH₃ CH₂CH₂—CO₂H  71. H OCH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃  72. H OCH₂C₆H₅ CH₃ CH₂CH₂—CO₂H  73. H OCH₂CH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃  74. H OCH₂CH₂C₆H₅ CH₃ CH₂CH₂—CO₂H  75. H OCH₂—CONH₂ HCH₂CH₂—CO₂CH₂CH₃  76. H OCH₂—CONH₂ CH₃ CH₂CH₂—CO₂H  77. H H HCH₂CH₂P—O(OCH₂CH₃)₂  78. H H CH₃ CH₂CH₂P—O(OH)₂  79. OH H HCH₂CH₂P—O(OCH₂CH₃)₂  80. OH H CH₃ CH₂CH₂P—O(OH)₂  81. OCH₃ H HCH₂CH₂P—O(OCH₂CH₃)₂  82. OCH₃ H CH₃ CH₂CH₂P—O(OH)₂  83. OCH₂CH═CH₂ H HCH₂CH₂P—O(OCH₂CH₃)₂  84. OCH₂CH═CH₂ H CH₃ CH₂CH₂P—O(OH)₂  85. OCH₂C₆H₅ HH CH₂CH₂P—O(OCH₂CH₃)₂  86. OCH₂C₆H₅ H CH₃ CH₂CH₂P—O(OH)₂  87.OCH₂CH₂C₆H₅ H H CH₂CH₂P—O(OCH₂CH₃)₂  88. OCH₂CH₂C₆H₅ H CH₃CH₂CH₂P—O(OH)₂  89. OCH₂—CONH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂  90. OCH₂—CONH₂ HCH₃ CH₂CH₂P—O(OH)₂  91. H Cl H CH₂CH₂P—O(OCH₂CH₃)₂  92. H Cl CH₃CH₂CH₂P—O(OH)₂  93. Br H H CH₂CH₂P—O(OCH₂CH₃)₂  94. Br H CH₃CH₂CH₂P—O(OH)₂  95. H CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂  96. H CH₃ CH₃CH₂CH₂P—O(OH)₂  97. NO₂ H H CH₂CH₂P—O(OCH₂CH₃)₂  98. NO₂ H CH₃CH₂CH₂P—O(OH)₂  99. NH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂ 100. NH₂ H CH₃CH₂CH₂P—O(OH)₂ 101. NHSO₂CH₃ H H CH₂CH₂P—O(OCH₂CH₃)₂ 102. NHSO₂CH₃ H CH₃CH₂CH₂P—O(OH)₂ 103. H OH H CH₂CH₂P—O(OCH₂CH₃)₂ 104. H OH CH₃CH₂CH₂P—O(OH)₂ 105. H OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ 106. H OCH₃ CH₃CH₂CH₂P—O(OH)₂ 107. H OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ 108. H OCH₂CH═CH₂CH₃ CH₂CH₂P—O(OH)₂ 109. H OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ 110. H OCH₂C₆H₅CH₃ CH₂CH₂P—O(OH)₂ 111. H OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ 112. HOCH₂CH₂C₆H₅ CH₃ CH₂CH₂P—O(OH)₂ 113. H OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂114. H OCH₂—CONH₂ CH₃ CH₂CH₂P—O(OH)₂ 115. H H H CH₂CH═CH—CO₂CH₂CH₃ 116.H H CH₃ CH₂CH═CH—CO₂H 117. OH H H CH₂CH═CH—CO₂CH₂CH₃ 118. OH H CH₃CH₂CH═CH—CO₂H 119. OCH₃ H H CH₂CH═CH—CO₂CH₂CH₃ 120. OCH₃ H CH₃CH₂CH═CH—CO₂H 121. OCH₂CH═CH₂ H H CH₂CH═CH—CO₂CH₂CH₃ 122. OCH₂CH═CH₂ HCH₃ CH₂CH═CH—CO₂H 123. OCH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃ 124. OCH₂C₆H₅ HCH₃ CH₂CH═CH—CO₂H 125. OCH₂CH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃ 126.OCH₂CH₂C₆H₅ H CH₃ CH₂CH═CH—CO₂H 127. OCH₂—CONH₂ H H CH₂CH═CH—CO₂CH₂CH₃128. OCH₂—CONH₂ H CH₃ CH₂CH═CH—CO₂H 129. H Cl H CH₂CH═CH—CO₂CH₂CH₃ 130.H Cl CH₃ CH₂CH═CH—CO₂H 131. Br H H CH₂CH═CH—CO₂CH₂CH₃ 132. Br H CH₃CH₂CH═CH—CO₂H 133. H CH₃ H CH₂CH═CH—CO₂CH₂CH₃ 134. H CH₃ CH₃CH₂CH═CH—CO₂H 135. NO₂ H H CH₂CH═CH—CO₂CH₂CH₃ 136. NO₂ H CH₃CH₂CH═CH—CO₂H 137. NH₂ H H CH₂CH═CH—CO₂CH₂CH₃ 138. NH₂ H CH₃CH₂CH═CH—CO₂H 139. NHSO₂CH₃ H H CH₂CH═CH—CO₂CH₂CH₃ 140. NHSO₂CH₃ H CH₃CH₂CH═CH—CO₂H 141. H OH H CH₂CH═CH—CO₂CH₂CH₃ 142. H OH CH₃ CH₂CH═CH—CO₂H143. H OCH₃ H CH₂CH═CH—CO₂CH₂CH₃ 144. H OCH₃ CH₃ CH₂CH═CH—CO₂H 145. HOCH₂CH═CH₂ H CH₂CH═CH—CO₂CH₂CH₃ 146. H OCH₂CH═CH₂ CH₃ CH₂CH═CH—CO₂H 147.H OCH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃ 148. H OCH₂C₆H₅ CH₃ CH₂CH═CH—CO₂H 149. HOCH₂CH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃ 150. H OCH₂CH₂C₆H₅ CH₃ CH₂CH═CH—CO₂H151. H OCH₂—CONH₂ H CH₂CH═CH—CO₂CH₂CH₃ 152. H OCH₂—CONH₂ CH₃CH₂CH═CH—CO₂H 153. H H CH₂—CO₂CH₂CH₃ CH₃ 154. H H CH₂—CO₂H CH₃ 155. OH HCH₂—CO₂CH₂CH₃ CH₃ 156. OH H CH₂—CO₂H CH₃ 157. OCH₃ H CH₂—CO₂CH₂CH₃ CH₃158. OCH₃ H CH₂—CO₂H CH₃ 159. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₃ 160.OCH₂CH═CH₂ H CH₂—CO₂H CH₃ 161. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃ 162.OCH₂C₆H₅ H CH₂—CO₂H CH₃ 163. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃ 164.OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₃ 165. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₃ 166.OCH₂—CONH₂ H CH₂—CO₂H CH₃ 167. H Cl CH₂—CO₂CH₂CH₃ CH₃ 168. H Cl CH₂—CO₂HCH₃ 169. Br H CH₂—CO₂CH₂CH₃ CH₃ 170. Br H CH₂—CO₂H CH₃ 171. H CH₃CH₂—CO₂CH₂CH₃ CH₃ 172. H CH₃ CH₂—CO₂H CH₃ 173. NO₂ H CH₂—CO₂CH₂CH₃ CH₃174. NO₂ H CH₂—CO₂H CH₃ 175. NH₂ H CH₂—CO₂CH₂CH₃ CH₃ 176. NH₂ H CH₂—CO₂HCH₃ 177. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₃ 178. NHSO₂CH₃ H CH₂—CO₂H CH₃ 179.H OH CH₂—CO₂CH₂CH₃ CH₃ 180. H OH CH₂—CO₂H CH₃ 181. H OCH₃ CH₂—CO₂CH₂CH₃CH₃ 182. H OCH₃ CH₂—CO₂H CH₃ 183. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ 184. HOCH₂CH═CH₂ CH₂—CO₂H CH₃ 185. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ 186. H OCH₂C₆H₅CH₂—CO₂H CH₃ 187. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ 188. H OCH₂CH₂C₆H₅CH₂—CO₂H CH₃ 189. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ 190. H OCH₂—CONH₂ CH₂—CO₂HCH₃ 191. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 192. H H CH₂CH₂P—O(OH)₂ CH₃ 193. OHH CH₂CH₂P—O(OCH₂CH₃₎ ₂ Ch₃ 194. OH H CH₂CH₂P—O(OH)₂ CH₃ 195. OCH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 196. OCH₃ H CH₂CH₂P—O(OH)₂ CH₃ 197. OCH₂CH═CH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 198. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₃ 199.OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 200. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₃201. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 202. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₃ 203. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 204.OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₃ 205. H Cl CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 206. HCl CH₂CH₂P—O(OH)₂ CH₃ 207. Br H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 208. Br HCH₂CH₂P—O(OH)₂ CH₃ 209. H CH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 210. H CH₃CH₂CH₂P—O(OH)₂ CH₃ 211. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 212. NO₂ HCH₂CH₂P—O(OH)₂ CH₃ 213. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 214. NH₂ HCH₂CH₂P—O(OH)₂ CH₃ 215. NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 216. NHSO₂CH₃H CH₂CH₂P—O(OH)₂ CH₃ 217. H OH CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 218. H OHCH₂CH₂P—O(OH)₂ CH₃ 219. H OCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 220. H OCH₃CH₂CH₂P—O(OH)₂ CH₃ 221. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 222. HOCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₃ 223. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃224. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₃ 225. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 226. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₃ 227. HOCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 228. H OCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₃229. H H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 230. H H CH₂—CO₂H CH₂CH═CH₂ 231. OH HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 232. OH H CH₂—CO₂H CH₂CH═CH₂ 233. OCH₃ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 234. OCH₃ H CH₂—CO₂H CH₂CH═CH₂ 235. OCH₂CH═CH₂ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 236. OCH₂CH═CH₂ H CH₂—CO₂H CH₂CH═CH₂ 237.OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 238. OCH₂C₆H₅ H CH₂—CO₂H CH₂CH═CH₂239. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 240. OCH₂CH₂C₆H₅ H CH₂—CO₂HCH₂CH═CH₂ 241. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 242. OCH₂—CONH₂ HCH₂—CO₂H CH₂CH═CH₂ 243. H Cl CH₂—CH₂CH₂CH₃ CH₂CH═CH₂ 244. H Cl CH₂—CO₂HCH₂CH═CH₂ 245. Br H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 246. Br H CH₂—CO₂H CH₂CH═CH₂247. H CH₃ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 248. H CH₃ CH₂—CO₂H CH₂CH═CH₂ 249.NO₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 250. NO₂ H CH₂—CO₂H CH₂CH═CH₂ 251. NH₂ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 252. NH₂ H CH₂—CO₂H CH₂CH═CH₂ 253. NHSO₂CH₃ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 254. NHSO₂CH₃ H CH₂—CO₂H CH₂CH═CH₂ 255. H OHCH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 256. H OH CH₂—CO₂H CH₂CH═CH₂ 257. H OCH₃CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 258. H OCH₃ CH₂—CO₂H CH₂CH═CH₂ 259. H OCH₂CH═CH₂CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 260. H OCH₂CH═CH₂ CH₂—CO₂H CH₂CH═CH₂ 261. HOCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 262. H OCH₂C₆H₅ CH₂—CO₂H CH₂CH═CH₂ 263.H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 264. H OCH₂CH₂C₆H₅ CH₂—CO₂HCH₂CH═CH₂ 265. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 266. H OCH₂—CONH₂CH₂—CO₂H CH₂CH═CH₂ 267. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 268. H HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 269. OH H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 270. OHH CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 271. OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂272. OCH₃ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 273. OCH₂CH═CH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 274. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂275. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 276. OCH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 277. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂ 278. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 279. OCH₂—CONH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 280. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂281. H Cl CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 282. H Cl CH₂CH₂P—O(OH)₂CH₂CH═CH₂ 283. Br H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 284. Br HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 285. H CH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 286. HCH₃ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 287. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂288. NO₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 289. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂ 290. NH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 291. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 292. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂293. H OH CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 294. H OH CH₂CH₂P—O(OH)₂CH₂CH═CH₂ 295. H OCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 296. H OCH₃CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 297. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂298. H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 299. H OCH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 300. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂301. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 302. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 303. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂304. H OCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 305. H H CH₂—CO₂CH₂CH₃CH₂—CONH₂ 306. H H CH₂—CO₂H CH₂—CONH₂ 307. OH H CH₂—CO₂CH₂CH₃ CH₂—CONH₂308. OH H CH₂—CO₂H CH₂—CONH₂ 309. OCH₃ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 310.OCH₃ H CH₂—CO₂H CH₂—CONH₂ 311. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 312.OCH₂CH═CH₂ H CH₂—CO₂H CH₂—CONH₂ 313. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂314. OCH₂C₆H₅ H CH₂—CO₂H CH₂—CONH₂ 315. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃CH₂—CONH₂ 316. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂—CONH₂ 317. OCH₂—CONH₂ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 318. OCH₂—CONH₂ H CH₂—CO₂H CH₂—CONH₂ 319. H ClCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 320. H Cl CH₂—CO₂H CH₂—CONH₂ 321. Br HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 322. Br H CH₂—CO₂H CH₂—CONH₂ 323. H CH₃CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 324. H CH₃ CH₂—CO₂H CH₂—CONH₂ 325. NO₂ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 326. NO₂ H CH₂—CO₂H CH₂—CONH₂ 327. NH₂ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 328. NH₂ H CH₂—CO₂H CH₂—CONH₂ 329. NHSO₂CH₃ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 330. NHSO₂CH₃ H CH₂—CO₂H CH₂—CONH₂ 331. H OHCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 332. H OH CH₂—CO₂H CH₂—CONH₂ 333. H OCH₃CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 334. H OCH₃ CH₂—CO₂H CH₂—CONH₂ 335. H OCH₂CH═CH₂CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 336. H OCH₂CH═CH₂ CH₂—CO₂H CH₂—CONH₂ 337. HOCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 338. H OCH₂C₆H₅ CH₂—CO₂H CH₂—CONH₂ 339.H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 340. H OCH₂CH₂C₆H₅ CH₂—CO₂HCH₂—CONH₂ 341. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 342. H OCH₂—CONH₂CH₂—CO₂H CH₂—CONH₂ 343. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 344. H HCH₂CH₂P—O(OH)₂ CH₂—CONH₂ 345. OH H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 346. OHH CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 347. OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂348. OCH₃ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 349. OCH₂CH═CH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 350. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂351. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 352. OCH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂—CONH₂ 353. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂—CONH₂ 354. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 355. OCH₂—CONH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 356. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂357. H Cl CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 358. H Cl CH₂CH₂P—O(OH)₂CH₂—CONH₂ 359. Br H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 360. Br HCH₂CH₂P—O(OH)₂ CH₂—CONH₂ 361. H CH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 362. HCH₃ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 363. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂364. NO₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 365. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂—CONH₂ 366. NH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 367. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 368. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂369. H OH CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 370. H OH CH₂CH₂P—O(OH)₂CH₂—CONH₂ 371. H OCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 372. H OCH₃CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 373. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂374. H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 375. H OCH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 376. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂377. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 378. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 379. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂380. H OCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 381. H H CH₂—CO₂CH₂CH₃CH₂C₆H₅ 382. H H CH₂—CO₂H CH₂C₆H₅ 383. OH H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 384.OH H CH₂—CO₂H CH₂C₆H₅ 385. OCH₃ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 386. OCH₃ HCH₂—CO₂H CH₂C₆H₅ 387. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 388. OCH₂CH═CH₂H CH₂—CO₂H CH₂C₆H₅ 389. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 390. OCH₂C₆H₅ HCH₂—CO₂H CH₂C₆H₅ 391. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 392.OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂C₆H₅ 393. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅394. OCH₂—CONH₂ H CH₂—CO₂H CH₂C₆H₅ 395. H Cl CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 396.H Cl CH₂—CO₂H CH₂C₆H₅ 397. Br H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 398. Br H CH₂—CO₂HCH₂C₆H₅ 399. H CH₃ CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 400. H CH₃ CH₂—CO₂H CH₂C₆H₅401. NO₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 402. NO₂ H CH₂—CO₂H CH₂C₆H₅ 403. NH₂ HCH₂—CO₂CH₂CH₃ CH₂C₆H₅ 404. NH₂ H CH₂—CO₂H CH₂C₆H₅ 405. NHSO₂CH₃ HCH₂—CO₂CH₂CH₃ CH₂C₆H₅ 406. NHSO₂CH₃ H CH₂—CO₂H CH₂C₆H₅ 407. H OHCH₂—CO₂CH₂CH₃ CH₂C₆H₅ 408. H OH CH₂—CO₂H CH₂C₆H₅ 409. H OCH₃CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 410. H OCH₃ CH₂—CO₂H CH₂C₆H₅ 411. H OCH₂CH═CH₂CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 412. H OCH₂CH═CH₂ CH₂—CO₂H CH₂C₆H₅ 413. H OCH₂C₆H₅CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 414. H OCH₂C₆H₅ CH₂—CO₂H CH₂C₆H₅ 415. HOCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 416. H OCH₂CH₂C₆H₅ CH₂—CO₂H CH₂C₆H₅417. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 418. H OCH₂—CONH₂ CH₂—CO₂HCH₂C₆H₅ 419. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 420. H H CH₂CH₂P—O(OH)₂CH₂C₆H₅ 421. OH H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 422. OH H CH₂CH₂P—O(OH)₂CH₂C₆H₅ 423. OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 424. OCH₃ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅ 425. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅426. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 427. OCH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 428. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 429.OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 430. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅ 431. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅432. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 433. H Cl CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 434. H Cl CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 435. Br H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 436. Br H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 437. H CH₃ CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 438. H CH₃ CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 439. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 440. NO₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 441. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 442. NH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 443. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 444. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 445.H OH CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 446. H OH CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 447. HOCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 448. H OCH₃ CH₂CH₂P—O(OH)₂ CH₂—CONH₂449. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 450. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 451. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂452. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 453. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 454. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂—CONH₂ 455. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 456. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂

TABLE IV

Ex. # X X¹ R¹ R”  1. H H H CH₂—CO₂CH₂CH₃  2. H H CH₃ CH₂—CO₂H  3. OH H HCH₂—CO₂CH₂CH₃  4. OH H CH₃ CH₂—CO₂H  5. OCH₃ H H CH₂—CO₂CH₂CH₃  6. OCH₃H CH₃ CH₂—CO₂H  7. OCH₂CH═CH₂ H H CH₂—CO₂CH₂CH₃  8. OCH₂CH═CH₂ H CH₃CH₂—CO₂H  9. OCH₂C₆H₅ H H CH₂—CO₂CH₂CH₃  10. OCH₂C₆H₅ H CH₃ CH₂—CO₂H 11. OCH₂CH₂C₆H₅ H H CH₂—CO₂CH₂CH₃  12. OCH₂CH₂C₆H₅ H CH₃ CH₂—CO₂H  13.OCH₂—CONH₂ H H CH₂—CO₂CH₂CH₃  14. OCH₂—CONH₂ H CH₃ CH₂—CO₂H  15. H CL HCH₂—CO₂CH₂CH₃  16. H Cl CH₃ CH₂—CO₂H  17. Br H H CH₂—CO₂CH₂CH₃  18. Br HCH₃ CH₂—CO₂H  19. H CH₃ H CH₂—CO₂CH₂CH₃  20. H CH₃ CH₃ CH₂—CO₂H  21. NO₂H H CH₂—CO₂CH₂CH₃  22. NO₂ H CH₃ CH₂—CO₂H  23. NH₂ H H CH₂—CO₂CH₂CH₃ 24. NH₂ H CH₃ CH₂—CO₂H  25. NHSO₂CH₃ H H CH₂—CO₂CH₂CH₃  26. NHSO₂CH₃ HCH₃ CH₂—CO₂H  27. H OH H CH₂—CO₂CH₂CH₃  28. H OH CH₃ CH₂—CO₂H  29. HOCH₃ H CH₂—CO₂CH₂CH₃  30. H OCH₃ CH₃ CH₂—CO₂H  31. H OCH₂CH═CH₂ HCH₂—CO₂CH₂CH₃  32. H OCH₂CH═CH₂ CH₃ CH₂—CO₂H  33. H OCH₂C₆H₅ HCH₂—CO₂CH₂CH₃  34. H OCH₂C₆H₅ CH₃ CH₂—CO₂H  35. H OCH₂CH₂C₆H₅ HCH₂—CO₂CH₂CH₃  36. H OCH₂CH₂C₆H₅ CH₃ CH₂—CO₂H  37. H OCH₂—CONH₂ HCH₂—CO₂CH₂CH₃  38. H OCH₂—CONH₂ CH₃ CH₂—CO₂H  39. H H H CH₂CH₂—CO₂CH₂CH₃ 40. H H CH₃ CH₂CH₂—CO₂H  41. OH H H CH₂CH₂—CO₂CH₂CH₃  42. OH H CH₃CH₂CH₂—CO₂H  43. OCH₃ H H CH₂CH₂—CO₂CH₂CH₃  44. OCH₃ H CH₃ CH₂CH₂—CO₂H 45. OCH₂CH═CH₂ H H CH₂CH₂—CO₂CH₂CH₃  46. OCH₂CH═CH₂ H CH₃ CH₂CH₂—CO₂H 47. OCH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃  48. OCH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H  49.OCH₂CH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃  50. OCH₂CH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H  51.OCH₂—CONH₂ H H CH₂CH₂—CO₂CH₂CH₃  52. OCH₂—CONH₂ H CH₃ CH₂CH₂—CO₂H  53. HCl H CH₂CH₂—CO₂CH₂CH₃  54. H Cl CH₃ CH₂CH₂—CO₂H  55. Br H HCH₂CH₂—CO₂CH₂CH₃  56. Br H CH₃ CH₂CH₂—CO₂H  57. H CH₃ H CH₂CH₂—CO₂CH₂CH₃ 58. H CH₃ CH₃ CH₂CH₂—CO₂H  59. NO₂ H H CH₂CH₂—CO₂CH₂CH₃  60. NO₂ H CH₃CH₂CH₂—CO₂H  61. NH₂ H H CH₂CH₂—CO₂CH₂CH₃  62. NH₂ H CH₃ CH₂CH₂—CO₂H 63. NHSO₂CH₃ H H CH₂CH₂—CO₂CH₂CH₃  64. NHSO₂CH₃ H CH₃ CH₂CH₂—CO₂H  65.H OH H CH₂CH₂—CO₂CH₂CH₃  66. H OH CH₃ CH₂CH₂—CO₂H  67. H OCH₃ HCH₂CH₂—CO₂CH₂CH₃  68. H OCH₃ CH₃ CH₂CH₂—CO₂H  69. H OCH₂CH═CH₂ HCH₂CH₂—CO₂CH₂CH₃  70. H OCH₂CH═CH₂ CH₃ CH₂CH₂—CO₂H  71. H OCH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃  72. H OCH₂C₆H₅ CH₃ CH₂CH₂—CO₂H  73. H OCH₂CH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃  74. H OCH₂CH₂C₆H₅ CH₃ CH₂CH₂—CO₂H  75. H OCH₂—CONH₂ HCH₂CH₂—CO₂CH₂CH₃  76. H OCH₂—CONH₂ CH₃ CH₂CH₂—CO₂H  77. H H HCH₂CH₂P—O(OCH₂CH₃)₂  78. H H CH₃ CH₂CH₂P—O(OH)₂  79. OH H HCH₂CH₂P—O(OCH₂CH₃)₂  80. OH H CH₃ CH₂CH₂P—O(OH)₂  81. OCH₃ H HCH₂CH₂P—O(OCH₂CH₃)₂  82. OCH₃ H CH₃ CH₂CH₂P—O(OH)₂  83. OCH₂CH═CH₂ H HCH₂CH₂P—O(OCH₂CH₃)₂  84. OCH₂CH═CH₂ H CH₃ CH₂CH₂P—O(OH)₂  85. OCH₂C₆H₅ HH CH₂CH₂P—O(OCH₂CH₃)₂  86. OCH₂C₆H₅ H CH₃ CH₂CH₂P—O(OH)₂  87.OCH₂CH₂C₆H₅ H H CH₂CH₂P—O(OCH₂CH₃)₂  88. OCH₂CH₂C₆H₅ H CH₃CH₂CH₂P—O(OH)₂  89. OCH₂—CONH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂  90. OCH₂—CONH₂ HCH₃ CH₂CH₂P—O(OH)₂  91. H Cl H CH₂CH₂P—O(OCH₂CH₃)₂  92. H Cl CH₃CH₂CH₂P—O(OH)₂  93. Br H H CH₂CH₂P—O(OCH₂CH₃)₂  94. Br H CH₃CH₂CH₂P—O(OH)₂  95. H CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂  96. H CH₃ CH₃CH₂CH₂P—O(OH)₂  97. NO₂ H H CH₂CH₂P—O(OCH₂CH₃)₂  98. NO₂ H CH₃CH₂CH₂P—O(OH)₂  99. NH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂ 100. NH₂ H CH₃CH₂CH₂P—O(OH)₂ 101. NHSO₂CH₃ H H CH₂CH₂P—O(OCH₂CH₃)₂ 102. NHSO₂CH₃ H CH₃CH₂CH₂P—O(OH)₂ 103. H OH H CH₂CH₂P—O(OCH₂CH₃)₂ 104. H OH CH₃CH₂CH₂P—O(OH)₂ 105. H OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ 106. H OCH₃ CH₃CH₂CH₂P—O(OH)₂ 107. H OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ 108. H OCH₂CH═CH₂CH₃ CH₂CH₂P—O(OH)₂ 109. H OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ 110. H OCH₂C₆H₅CH₃ CH₂CH₂P—O(OH)₂ 111. H OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ 112. HOCH₂CH₂C₆H₅ CH₃ CH₂CH₂P—O(OH)₂ 113. H OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂114. H OCH₂—CONH₂ CH₃ CH₂CH₂P—O(OH)₂ 115. H H H CH₂CH═CH—CO₂CH₂CH₃ 116.H H CH₃ CH₂CH═CH—CO₂H 117. OH H H CH₂CH═CH—CO₂CH₂CH₃ 118. OH H CH₃CH₂CH═CH—CO₂H 119. OCH₃ H H CH₂CH═CH—CO₂CH₂CH₃ 120. OCH₃ H CH₃CH₂CH═CH—CO₂H 121. OCH₂CH═CH₂ H H CH₂CH═CH—CO₂CH₂CH₃ 122. OCH₂CH═CH₂ HCH₃ CH₂CH═CH—CO₂H 123. OCH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃ 124. OCH₂C₆H₅ HCH₃ CH₂CH═CH—CO₂H 125. OCH₂CH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃ 126.OCH₂CH₂C₆H₅ H CH₃ CH₂CH═CH—CO₂H 127. OCH₂—CONH₂ H H CH₂CH═CH—CO₂CH₂CH₃128. OCH₂—CONH₂ H CH₃ CH₂CH═CH—CO₂H 129. H Cl H CH₂CH═CH—CO₂CH₂CH₃ 130.H Cl CH₃ CH₂CH═CH—CO₂H 131. Br H H CH₂CH═CH—CO₂CH₂CH₃ 132. Br H CH₃CH₂CH═CH—CO₂H 133. H CH₃ H CH₂CH═CH—CO₂CH₂CH₃ 134. H CH₃ CH₃CH₂CH═CH—CO₂H 135. NO₂ H H CH₂CH═CH—CO₂CH₂CH₃ 136. NO₂ H CH₃CH₂CH═CH—CO₂H 137. NH₂ H H CH₂CH═CH—CO₂CH₂CH₃ 138. NH₂ H CH₃CH₂CH═CH—CO₂H 139. NHSO₂CH₃ H H CH₂CH═CH—CO₂CH₂CH₃ 140. NHSO₂CH₃ H CH₃CH₂CH═CH—CO₂H 141. H OH H CH₂CH═CH—CO₂CH₂CH₃ 142. H OH CH₃ CH₂CH═CH—CO₂H143. H OCH₃ H CH₂CH═CH—CO₂CH₂CH₃ 144. H OCH₃ CH₃ CH₂CH═CH—CO₂H 145. HOCH₂CH═CH₂ H CH₂CH═CH—CO₂CH₂CH₃ 146. H OCH₂CH═CH₂ CH₃ CH₂CH═CH—CO₂H 147.H OCH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃ 148. H OCH₂C₆H₅ CH₃ CH₂CH═CH—CO₂H 149. HOCH₂CH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃ 150. H OCH₂CH₂C₆H₅ CH₃ CH₂CH═CH—CO₂H151. H OCH₂—CONH₂ H CH₂CH═CH—CO₂CH₂CH₃ 152. H OCH₂—CONH₂ CH₃CH₂CH═CH—CO₂H 153. H H CH₂—CO₂CH₂CH₃ CH₃ 154. H H CH₂—CO₂H CH₃ 155. OH HCH₂—CO₂CH₂CH₃ CH₃ 156. OH H CH₂—CO₂H CH₃ 157. OCH₃ H CH₂—CO₂CH₂CH₃ CH₃158. OCH₃ H CH₂—CO₂H CH₃ 159. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₃ 160.OCH₂CH═CH₂ H CH₂—CO₂H CH₃ 161. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃ 162.OCH₂C₆H₅ H CH₂—CO₂H CH₃ 163. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃ 164.OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₃ 165. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₃ 166.OCH₂—CONH₂ H CH₂—CO₂H CH₃ 167. H Cl CH₂—CO₂CH₂CH₃ CH₃ 168. H Cl CH₂—CO₂HCH₃ 169. Br H CH₂—CO₂CH₂CH₃ CH₃ 170. Br H CH₂—CO₂H CH₃ 171. H CH₃CH₂—CO₂CH₂CH₃ CH₃ 172. H CH₃ CH₂—CO₂H CH₃ 173. NO₂ H CH₂—CO₂CH₂CH₃ CH₃174. NO₂ H CH₂—CO₂H CH₃ 175. NH₂ H CH₂—CO₂CH₂CH₃ CH₃ 176. NH₂ H CH₂—CO₂HCH₃ 177. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₃ 178. NHSO₂CH₃ H CH₂—CO₂H CH₃ 179.H OH CH₂—CO₂CH₂CH₃ CH₃ 180. H OH CH₂—CO₂H CH₃ 181. H OCH₃ CH₂—CO₂CH₂CH₃CH₃ 182. H OCH₃ CH₂CO₂H CH₃ 183. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₃ 184. HOCH₂CH═CH₂ CH₂—CO₂H CH₃ 185. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₃ 186. HOCH₂C₆H₅ CH₂—CO₂H CH₃ 187. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₃ 188. HOCH₂CH₂C₆H₅ CH₂—CO₂H CH₃ 189. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₃ 190. HOCH₂—CONH₂ CH₂—CO₂H CH₃ 191. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 192. H HCH₂CH₂P—O(OH)₂ CH₃ 193. OH H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 194. OH HCH₂CH₂P—O(OH)₂ CH₃ 195. OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 196. OCH₃ HCH₂CH₂P—O(OH)₂ CH₃ 197. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 198.OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₃ 199. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃200. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₃ 201. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 202. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₃ 203.OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 204. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂CH₃ 205. H Cl CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 206. H Cl CH₂CH₂P—O(OH)₂ CH₃ 207.Br H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 208. Br H CH₂CH₂P—O(OH)₂ CH₃ 209. H CH₃CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 210. H CH₃ CH₂CH₂P—O(OH)₂ CH₃ 211. NO₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 212. NO₂ H CH₂CH₂P—O(OH)₂ CH₃ 213. NH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 214. NH₂ H CH₂CH₂P—O(OH)₂ CH₃ 215. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 216. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₃ 217. H OHCH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 218. H OH CH₂CH₂P—O(OH)₂ CH₃ 219. H OCH₃CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 220. H OCH₃ CH₂CH₂P—O(OH)₂ CH₃ 221. H OCH₂CH═CH₂CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 222. H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₃ 223. HOCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 224. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₃ 225.H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 226. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₃ 227. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 228. H OCH₂—CONH₂CH₂CH₂P—O(OH)₂ CH₃ 229. H H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 230. H H CH₂—CO₂HCH₂CH═CH₂ 231. OH H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 232. OH H CH₂—CO₂H CH₂CH═CH₂233. OCH₃ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 234. OCH₃ H CH₂—CO₂H CH₂CH═CH₂ 235.OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 236. OCH₂CH═CH₂ H CH₂—CO₂HCH₂CH═CH₂ 237. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 238. OCH₂C₆H₅ HCH₂—CO₂H CH₂CH═CH₂ 239. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 240.OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂CH═CH₂ 241. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃CH₂CH═CH₂ 242. OCH₂—CONH₂ H CH₂—CO₂H CH₂CH═CH₂ 243. H Cl CH₂—CO₂CH₂CH₃CH₂CH═CH₂ 244. H Cl CH₂—CO₂H CH₂CH═CH₂ 245. Br H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂246. Br H CH₂—CO₂H CH₂CH═CH₂ 247. H CH₃ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 248. HCH₃ CH₂—CO₂H CH₂CH═CH₂ 249. NO₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 250. NO₂ HCH₂—CO₂H CH₂CH═CH₂ 251. NH₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 252. NH₂ HCH₂—CO₂H CH₂CH═CH₂ 253. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 254. NHSO₂CH₃H CH₂—CO₂H CH₂CH═CH₂ 255. H OH CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 256. H OHCH₂—CO₂H CH₂CH═CH₂ 257. H OCH₃ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 258. H OCH₃CH₂—CO₂H CH₂CH═CH₂ 259. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 260. HOCH₂CH═CH₂ CH₂—CO₂H CH₂CH═CH₂ 261. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂262. H OCH₂C₆H₅ CH₂—CO₂H CH₂CH═CH₂ 263. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃CH₂CH═CH₂ 264. H OCH₂CH₂C₆H₅ CH₂—CO₂H CH₂CH═CH₂ 265. H OCH₂—CONH₂CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 266. H OCH₂—CONH₂ CH₂—CO₂H CH₂CH═CH₂ 267. H HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 268. H H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 269. OHH CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 270. OH H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 271.OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 272. OCH₃ H CH₂CH₂P—O(OH)₂CH₂CH═CH₂ 273. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 274.OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 275. OCH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 276. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂277. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 278. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 279. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂280. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 281. H Cl CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂ 282. H Cl CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 283. Br HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 284. Br H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 285. HCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 286. H CH₃ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂287. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 288. NO₂ H CH₂CH₂P—O(OH)₂CH₂CH═CH₂ 289. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 290. NH₂ HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 291. NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂292. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 293. H OH CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂ 294. H OH CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 295. H OCH₃CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 296. H OCH₃ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 297.H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 298. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 299. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂300. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 301. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 302. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂CH═CH₂ 303. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 304. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 305. H H CH₂—CO₂CH₂CH₃ CH₂—CONH₂306. H H CH₂—CO₂H CH₂—CONH₂ 307. OH H CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 308. OH HCH₂—CO₂H CH₂—CONH₂ 309. OCH₃ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 310. OCH₃ HCH₂—CO₂H CH₂—CONH₂ 311. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 312.OCH₂CH═CH₂ H CH₂—CO₂H CH₂—CONH₂ 313. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂314. OCH₂C₆H₅ H CH₂—CO₂H CH₂—CONH₂ 315. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃CH₂—CONH₂ 316. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂—CONH₂ 317. OCH₂—CONH₂ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 318. OCH₂—CONH₂ H CH₂—CO₂H CH₂—CONH₂ 319. H ClCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 320. H Cl CH₂—CO₂H CH₂—CONH₂ 321. Br HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 322. Br H CH₂—CO₂H CH₂—CONH₂ 323. H CH₃CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 324. H CH₃ CH₂—CO₂H CH₂—CONH₂ 325. NO₂ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 326. NO₂ H CH₂—CO₂H CH₂—CONH₂ 327. NH₂ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 328. NH₂ H CH₂—CO₂H CH₂—CONH₂ 329. NHSO₂CH₃ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 330. NHSO₂CH₃ H CH₂—CO₂H CH₂—CONH₂ 331. H OHCH₂—CO₂CH₂CH₃ CH₂—CONH₂ 332. H OH CH₂—CO₂H CH₂—CONH₂ 333. H OCH₃CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 334. H OCH₃ CH₂—CO₂H CH₂—CONH₂ 335. H OCH₂CH═CH₂CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 336. H OCH₂CH═CH₂ CH₂—CO₂H CH₂—CONH₂ 337. HOCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 338. H OCH₂C₆H₅ CH₂—CO₂H CH₂—CONH₂ 339.H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 340. H OCH₂CH₂C₆H₅ CH₂—CO₂HCH₂—CONH₂ 341. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂—CONH₂ 342. H OCH₂—CONH₂CH₂—CO₂H CH₂—CONH₂ 343. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 344. H HCH₂CH₂P—O(OH)₂ CH₂—CONH₂ 345. OH H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 346. OHH CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 347. OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂348. OCH₃ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 349. OCH₂CH═CH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 350. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂351. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 352. OCH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂—CONH₂ 353. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂—CONH₂ 354. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 355. OCH₂—CONH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 356. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂357. H Cl CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 358. H Cl CH₂CH₂P—O(OH)₂CH₂—CONH₂ 359. Br H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 360. Br HCH₂CH₂P—O(OH)₂ CH₂—CONH₂ 361. H CH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 362. HCH₃ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 363. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂364. NO₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 365. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂—CONH₂ 366. NH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 367. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 368. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂369. H OH CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 370. H OH CH₂CH₂P—O(OH)₂CH₂—CONH₂ 371. H OCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 372. H OCH₃CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 373. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂374. H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 375. H OCH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 376. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂377. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 378. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 379. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂380. H OCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 381. H H CH₂—CO₂CH₂CH₃CH₂C₆H₅ 382. H H CH₂—CO₂H CH₂C₆H₅ 383. OH H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 384.OH H CH₂—CO₂H CH₂C₆H₅ 385. OCH₃ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 386. OCH₃ HCH₂—CO₂H CH₂C₆H₅ 387. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 388. OCH₂CH═CH₂H CH₂—CO₂H CH₂C₆H₅ 389. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 390. OCH₂C₆H₅ HCH₂—CO₂H CH₂C₆H₅ 391. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 392.OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂C₆H₅ 393. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅394. OCH₂—CONH₂ H CH₂—CO₂H CH₂C₆H₅ 395. H Cl CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 396.H Cl CH₂—CO₂H CH₂C₆H₅ 397. Br H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 398. Br H CH₂—CO₂HCH₂C₆H₅ 399. H CH₃ CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 400. H CH₃ CH₂—CO₂H CH₂C₆H₅401. NO₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 402. NO₂ H CH₂—CO₂H CH₂C₆H₅ 403. NH₂ HCH₂—CO₂CH₂CH₃ CH₂C₆H₅ 404. NH₂ H CH₂—CO₂H CH₂C₆H₅ 405. NHSO₂CH₃ HCH₂—CO₂CH₂CH₃ CH₂C₆H₅ 406. NHSO₂CH₃ H CH₂—CO₂H CH₂C₆H₅ 407. H OHCH₂—CO₂CH₂CH₃ CH₂C₆H₅ 408. H OH CH₂—CO₂H CH₂C₆H₅ 409. H OCH₃CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 410. H OCH₃ CH₂—CO₂H CH₂C₆H₅ 411. H OCH₂CH═CH₂CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 412. H OCH₂CH═CH₂ CH₂—CO₂H CH₂C₆H₅ 413. H OCH₂C₆H₅CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 414. H OCH₂C₆H₅ CH₂—CO₂H CH₂C₆H₅ 415. HOCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 416. H OCH₂CH₂C₆H₅ CH₂—CO₂H CH₂C₆H₅417. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂C₆H₅ 418. H OCH₂—CONH₂ CH₂—CO₂HCH₂C₆H₅ 419. H H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 420. H H CH₂CH₂P—O(OH)₂CH₂C₆H₅ 421. OH H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 422. OH H CH₂CH₂P—O(OH)₂CH₂C₆H₅ 423. OCH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 424. OCH₃ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅ 425. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅426. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 427. OCH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 428. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 429.OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 430. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅ 431. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅432. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 433. H Cl CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 434. H Cl CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 435. Br H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 436. Br H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 437. H CH₃ CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 438. H CH₃ CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 439. NO₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 440. NO₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 441. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅ 442. NH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 443. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 444. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 445.H OH CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 446. H OH CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 447. HOCH₃ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 448. H OCH₃ CH₂CH₂P—O(OH)₂ CH₂—CONH₂449. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 450. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 451. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂452. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂ 453. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 454. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂—CONH₂ 455. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 456. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂

TABLE Va

Ex. # X X¹ X² X³ R¹ 1. OCH₂CO₂—CH₂CH₃ H H H H 2. OCH₂CO₂—CH₂CH₃ H H HCH₃ 3. OCH₂CO₂H H H H H 4. OCH₂CO₂H H H H CH₃ 5. OCH₂CH₂—CO₂CH₂CH₃ H H HH 6. OCH₂CH₂—CO₂CH₂CH₃ H H H CH₃ 7. OCH₂CH₂—CO₂H H H H H 8. OCH₂CH₂—CO₂HH H H CH₃ 9. OCH₂CH═CH—CO₂CH₂CH₃ H H H H 10. OCH₂CH═CH—CO₂CH₂CH₃ H H HCH₃ 11. OCH₂CH═CH—CO₂H H H H H 12. OCH₂CH═CH—CO₂H H H H CH₃ 13.OCH₂CH₂—PO(OCH₂CH₃)₂ H H H H 14. OCH₂CH₂—PO(OCH₂CH₃)₂ H H H CH₃ 15.OCH₂CH₂—PO(OH)₂ H H H H 16. OCH₂CH₂—PO(OH)₂ H H H CH₃ 17. HOCH₂CO₂—CH₂CH₃ H H H 18. H OCH₂CO₂—CH₂CH₃ H H CH₃ 19. H OCH₂CO₂H H H H20. H OCH₂CO₂H H H CH₃ 21. H OCH₂CH₂CO₂—CH₂CH₃ H H H 22. HOCH₂CH₂CO₂—CH₂CH₃ H H CH₃ 23. H OCH₂CH₂CO₂H H H H 24. H OCH₂CH₂CO₂H H HCH₃ 25. H OCH₂CH═CH—CO₂CH₂CH₃ H H H 26. H OCH₂CH═CH—CO₂CH₂CH₃ H H CH₃27. H OCH₂CH═CH—CO₂H H H H 28. H OCH₂CH═CH—CO₂H H H CH₃ 29. HOCH₂CH₂—PO(OCH₂CH₃)₂ H H H 30. H OCH₂CH₂—PO(OCH₂CH₃)₂ H H CH₃ 31. HOCH₂CH₂—PO(OH)₂ H H H 32. H OCH₂CH₂—PO(OH)₂ H H CH₃ 33. H HOCH₂CO₂—CH₂CH₃ H H 34. H H OCH₂CO₂—CH₂CH₃ H CH₃ 35. H H OCH₂CO₂H H H 36.H H OCH₂CO₂H H CH₃ 37. H H OCH₂CH₂—CO₂CH₂CH₃ H H 38. H HOCH₂CH₂—CO₂CH₂CH₃ H CH₃ 39. H H OCH₂CH₂—CO₂H H H 40. H H OCH₂CH₂—CO₂H HCH₃ 41. H H OCH₂—CH═CH—CO₂CH₂CH₃ H H 42. H H OCH₂—CH═CH—CO₂CH₂CH₃ H CH₃43. H H OCH₂—CH═CHCO₂H H H 44. H H OCH₂—CH═CHCO₂H H CH₃ 45. H HOCH₂CH₂PO—(OCH₂CH₃)₂ H H 46. H H OCH₂CH₂PO—(OCH₂CH₃)₂ H CH₃ 47. H HOCH₂CH₂—PO(OH)₂ H H 48. H H OCH₂CH₂—PO(OH)₂ H CH₃ 49. H H HOCH₂CO₂—CH₂CH₃ H 50. H H H OCH₂CO₂—CH₂CH₃ CH₃ 51. H H H OCH₂CO₂H H 52. HH H OCH₂CO₂H CH₃ 53. H H H OCH₂CH₂—CO₂CH₂CH₃ H 54. H H HOCH₂CH₂—CO₂CH₂CH₃ CH₃ 55. H H H OCH₂CH₂—CO₂H H 56. H H H OCH₂CH₂—CO₂HCH₃ 57. H H H OCH₂—CH═CH—CO₂CH₂CH₃ H 58. H H H OCH₂—CH═CH—CO₂CH₂CH₃ CH₃59. H H H OCH₂—CH═CHCO₂H H 60. H H H OCH₂—CH═CHCO₂H CH₃ 61. H H HOCH₂CH₂PO—(OCH₂CH₃)₂ H 62. H H H OCH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 63. H H HOCH₂CH₂—PO(OH)₂ H 64. H H H OCH₂CH₂—PO(OH)₂ CH₃

TABLE Vb

Ex. # X X¹ X² X³ R¹ 1. OCH₂CO₂—CH₂CH₃ H H H H 2. OCH₂CO₂—CH₂CH₃ H H HCH₃ 3. OCH₂CO₂H H H H H 4. OCH₂CO₂H H H H CH₃ 5. OCH₂CH₂—CO₂CH₂CH₃ H H HH 6. OCH₂CH₂—CO₂CH₂CH₃ H H H CH₃ 7. OCH₂CH₂—CO₂H H H H H 8. OCH₂CH₂—CO₂HH H H CH₃ 9. OCH₂CH═CH—CO₂CH₂CH₃ H H H H 10. OCH₂CH═CH—CO₂CH₂CH₃ H H HCH₃ 11. OCH₂CH═CH—CO₂H H H H H 12. OCH₂CH═CH—CO₂H H H H CH₃ 13.OCH₂CH₂—PO(OCH₂CH₃)₂ H H H H 14. OCH₂CH₂—PO(OCH₂CH₃)₂ H H H CH₃ 15.OCH₂CH₂—PO(OH)₂ H H H H 16. OCH₂CH₂—PO(OH)₂ H H H CH₃ 17. HOCH₂CO₂—CH₂CH₃ H H H 18. H OCH₂CO₂—CH₂CH₃ H H CH₃ 19. H OCH₂CO₂H H H H20. H OCH₂CO₂H H H CH₃ 21. H OCH₂CH₂CO₂—CH₂CH₃ H H H 22. HOCH₂CH₂CO₂—CH₂CH₃ H H CH₃ 23. H OCH₂CH₂CO₂H H H H 24. H OCH₂CH₂CO₂H H HCH₃ 25. H OCH₂CH═CH—CO₂CH₂CH₃ H H H 26. H OCH₂CH═CH—CO₂CH₂CH₃ H H CH₃27. H OCH₂CH═CH—CO₂H H H H 28. H OCH₂CH═CH—CO₂H H H CH₃ 29. HOCH₂CH₂—PO(OCH₂CH₃)₂ H H H 30. H OCH₂CH₂—PO(OCH₂CH₃)₂ H H CH₃ 31. HOCH₂CH₂—PO(OH)₂ H H H 32. H OCH₂CH₂—PO(OH)₂ H H CH₃ 33. H HOCH₂CO₂—CH₂CH₃ H H 34. H H OCH₂CO₂—CH₂CH₃ H CH₃ 35. H H OCH₂CO₂H H H 36.H H OCH₂CO₂H H CH₃ 37. H H OCH₂CH₂—CO₂CH₂CH₃ H H 38. H HOCH₂CH₂—CO₂CH₂CH₃ H CH₃ 39. H H OCH₂CH₂—CO₂H H H 40. H H OCH₂CH₂—CO₂H HCH₃ 41. H H OCH₂—CH═CH—CO₂CH₂CH₃ H H 42. H H OCH₂—CH═CH—CO₂CH₂CH₃ H CH₃43. H H OCH₂—CH═CHCO₂H H H 44. H H OCH₂—CH═CHCO₂H H CH₃ 45. H HOCH₂CH₂PO—(OCH₂CH₃)₂ H H 46. H H OCH₂CH₂PO—(OCH₂CH₃)₂ H CH₃ 47. H HOCH₂CH₂—PO(OH)₂ H H 48. H H OCH₂CH₂—PO(OH)₂ H CH₃ 49. H H HOCH₂CO₂—CH₂CH₃ H 50. H H H OCH₂CO₂—CH₂CH₃ CH₃ 51. H H H OCH₂CO₂H H 52. HH H OCH₂CO₂H CH₃ 53. H H H OCH₂CH₂—CO₂CH₂CH₃ H 54. H H HOCH₂CH₂—CO₂CH₂CH₃ CH₃ 55. H H H OCH₂CH₂—CO₂H H 56. H H H OCH₂CH₂—CO₂HCH₃ 57. H H H OCH₂—CH═CH—CO₂CH₂CH₃ H 58. H H H OCH₂—CH═CH—CO₂CH₂CH₃ CH₃59. H H H OCH₂—CH═CHCO₂H H 60. H H H OCH₂—CH═CHCO₂H CH₃ 61. H H HOCH₂CH₂PO—(OCH₂CH₃)₂ H 62. H H H OCH₂CH₂PO—(OCH₂CH₃)₂ CH₃ 63. H H HOCH₂CH₂—PO(OH)₂ H 64. H H H OCH₂CH₂—PO(OH)₂ CH₃

TABLE VIa

Ex. # X X¹ X² R A⁻ 1. H H H CH₃ Cl⁻ 2. H H H CH₂C≡CH Cl⁻ 3. H OCH₃ H CH₃Cl⁻ 4. H OCH₃ H CH₂C≡CH Cl⁻ 5. H H OCH₃ CH₃ Cl⁻ 6. H H OCH₃ CH₂C≡CH Cl⁻7. OCH₃ H H CH₃ Cl⁻ 8. OCH₃ H H CH₂C≡CH Cl⁻ 9. H OCH₂C₆H₅ H CH₃ Cl⁻ 10.H OCH₂C₆H₅ H CH₂C≡CH Cl⁻ 11. H H OCH₂C₆H₅ CH₃ Cl⁻ 12. H H OCH₂C₆H₅CH₂C≡CH Cl⁻ 13. OCH₂C₆H₅ H H CH₃ Cl⁻ 14. OCH₂C₆H₅ H H CH₂C≡CH Cl⁻ 15. HCl H CH₃ Cl⁻ 16. H Cl H CH₂C≡CH Cl⁻ 17. H H Cl CH₃ Cl⁻ 18. H H ClCH₂C≡CH Cl⁻ 19. Cl H H CH₃ Cl⁻ 20. Cl H H CH₂C≡CH Cl⁻ 21. H OH H CH₃ Cl⁻22. H OH H CH₂C≡CH Cl⁻ 23. H H OH CH₃ Cl⁻ 24. H H OH CH₂C≡CH Cl⁻ 25. OHH H CH₃ Cl⁻ 26. OH H H CH₂C≡CH Cl⁻ 27. H OCH₂CH═CH₂ H CH₃ Cl⁻ 28. HOCH₂CH═CH₂ H CH₂C≡CH Cl⁻ 29. H H OCH₂CH═CH₂ CH₃ Cl⁻ 30. H H OCH₂CH═CH₂CH₂C≡CH Cl⁻ 31. OCH₂CH═CH₂ H H CH₃ Cl⁻ 32. OCH₂CH═CH₂ H H CH₂C≡CH Cl⁻33. H NO₂ H CH₃ Cl⁻ 34. H NO₂ H CH₂C≡CH Cl⁻ 35. H H NO₂ CH₃ Cl⁻ 36. H HNO₂ CH₂C≡CH Cl⁻ 37. NO₂ H H CH₃ Cl⁻ 38. NO₂ H H CH₂C≡CH Cl⁻ 39. HNHSO₂CH₃ H CH₃ Cl⁻ 40. H NHSO₂CH₃ H CH₂C≡CH Cl⁻ 41. H H NHSO₂CH₃ CH₃ Cl⁻42. H H NHSO₂CH₃ CH₂C≡CH Cl⁻ 43. NHSO₂CH₃ H H CH₃ Cl⁻ 44. NHSO₂CH₃ H HCH₂C≡CH Cl⁻ 45. H H OCH₂CONH₂ CH₃ Cl⁻ 46. H H OCH₂CONH₂ CH₂C≡CH Cl⁻ 47.H OCH₂CONH₂ H CH₃ Cl⁻ 48. H OCH₂CONH₂ H CH₂C≡CH Cl⁻ 49. OCH₂CONH₂ H HCH₃ Cl⁻ 50. OCH₂CONH₂ H H CH₂C≡CH Cl⁻ 51. H OCH₂CH₂C₆H₅ H CH₃ Cl⁻ 52. HOCH₂CH₂C₆H₅ H CH₂C≡CH Cl⁻ 53. H H OCH₂CH₂C₆H₅ CH₃ Cl⁻ 54. H HOCH₂CH₂C₆H₅ CH₂C≡CH Cl 55. OCH₂CH₂C₆H₅ H H CH₃ Cl 56. OCH₂CH₂C₆H₅ H HCH₂C≡CH Cl 57. H OCH₂C₆H₄—Cl(3) H CH₃ Cl 58. H OCH₂C₆H₄—Cl(3) H CH₂C≡CHCl 59. H H OCH₂C₆H₄—Cl(3) CH₃ Cl 60. H H OCH₂C₆H₄—Cl(3) CH₂C≡CH Cl 61.OCH₂C₆H₄—Cl(3) H H CH₃ Cl 62. OCH₂C₆H₄—Cl(3) H H CH₂C≡CH Cl 63. HOCH₂C₆H₄—Cl(4) H CH₃ Cl 64. H OCH₂C₆H₄—Cl(4) H CH₂C≡CH Cl 65. H HOCH₂C₆H₄—Cl(4) CH₃ Cl 66. H H OCH₂C₆H₄—Cl(4) CH₂C≡CH Cl 67.OCH₂C₆H₄—Cl(4) H H CH₃ Cl 68. OCH₂C₆H₄—Cl(4) H H CH₂C≡CH Cl 69. HOCH₂C₆H₄CF₃(3) H CH₃ Cl 70. H OCH₂C₆H₄CF₃(3) H CH₂C≡CH Cl 71.OCH₂C₆H₄CF₃(3) H H CH₃ Cl 72. OCH₂C₆H₄CF₃(3) H H CH₂C≡CH Cl 73. H HOCH₂C₆H₄CF₃(3) CH₃ Cl 74. H H OCH₂C₆H₄CF₃(3) CH₂C≡CH Cl 75. HOCH₂C₆H₄CF₃(4) H CH₃ Cl 76. H OCH₂C₆H₄CF₃(4) H CH₂C≡CH Cl 77.OCH₂C₆H₄CF₃(4) H H CH₃ Cl 78. OCH₂C₆H₄CF₃(4) H H CH₂C≡CH Cl 79. H HOCH₂C₆H₄CF₃(4) CH₃ Cl 80. H H OCH₂C₆H₄CF₃(4) CH₂C≡CH Cl

TABLE VIb

Ex. # X X¹ X² R¹ 1. H H H H 2. H H H CH₃ 3. H OCH₃ H H 4. H OCH₃ H CH₃5. H H OCH₃ H 6. H H OCH₃ CH₃ 7. OCH₃ H H H 8. OCH₃ H H CH₃ 9. HOCH₂C₆H₅ H H 10. H OCH₂C₆H₅ H CH₃ 11. H H OCH₂C₆H₅ H 12. H H OCH₂C₆H₅CH₃ 13. OCH₂C₆H₅ H H H 14. OCH₂C₆H₅ H H CH₃ 15. H Cl H H 16. H Cl H CH₃17. H H Cl H 18. H H Cl CH₃ 19. Cl H H H 20. Cl H H CH₃ 21. H OH H H 22.H OH H CH₃ 23. H H OH H 24. H H OH CH₃ 25. OH H H H 26. OH H H CH₃ 27. HOCH₂CH═CH₂ H H 28. H OCH₂CH═CH₂ H CH₃ 29. H H OCH₂CH═CH₂ H 30. H HOCH₂CH═CH₂ CH₃ 31. OCH₂CH═CH₂ H H H 32. OCH₂CH═CH₂ H H CH₃ 33. H NO₂ H H34. H NO₂ H CH₃ 35. H H NO₂ H 36. H H NO₂ CH₃ 37. NO₂ H H H 38. NO₂ H HCH₃ 39. H NHSO₂CH₃ H H 40. H NHSO₂CH₃ H CH₃ 41. H H NHSO₂CH₃ H 42. H HNHSO₂CH₃ CH₃ 43. NHSO₂CH₃ H H H 44. NHSO₂CH₃ H H CH₃ 45. H H OCH₂CONH₂ H46. H H OCH₂CONH₂ CH₃ 47. H OCH₂CONH₂ H H 48. H OCH₂CONH₂ H CH₃ 49.OCH₂CONH₂ H H H 50. OCH₂CONH₂ H H CH₃ 51. H OCH₂CH₂C₆H₅ H H 52. HOCH₂CH₂C₆H₅ H CH₃ 53. H H OCH₂CH₂C₆H₅ H 54. H H OCH₂CH₂C₆H₅ CH₃ 55.OCH₂CH₂C₆H₅ H H H 56. OCH₂CH₂C₆H₅ H H CH₃ 57. H OCH₂C₆H₄—Cl(3) H H 58. HOCH₂C₆H₄—Cl(3) H CH₃ 59. H H OCH₂C₆H₄—Cl(3) H 60. H H OCH₂C₆H₄—Cl(3) CH₃61. OCH₂C₆H₄—Cl(3) H H H 62. OCH₂C₆H₄—Cl(3) H H CH₃ 63. H OCH₂C₆H₄—Cl(4)H H 64. H OCH₂C₆H₄—Cl(4) H CH₃ 65. H H OCH₂C₆H₄—Cl(4) CH₃ 66. H HOCH₂C₆H₄—Cl(4) H 67. OCH₂C₆H₄—Cl(4) H H CH₃ 68. OCH₂C₆H₄—Cl(4) H H H 69.H OCH₂C₆H₄CF₃(3) H H 70. H OCH₂C₆H₄CF₃(3) H CH₃ 71. OCH₂C₆H₄CF₃(3) H H H72. OCH₂C₆H₄CF₃(3) H H CH₃ 73. H H OCH₂C₆H₄CF₃(3) H 74. H HOCH₂C₆H₄CF₃(3) CH₃ 75. H OCH₂C₆H₄CF₃(4) H H 76. H OCH₂C₆H₄CF₃(4) H CH₃77. OCH₂C₆H₄CF₃(4) H H H 78. OCH₂C₆H₄CF₃(4) H H CH₃ 79. H HOCH₂C₆H₄CF₃(4) H 80. H H OCH₂C₆H₄CF₃(4) CH₃

TABLE VIIa

Ex. # X X¹ X² R 1. OCH₂CH═CH₂ H H H 2. OCH₂CH═CH₂ H H CH₃ 3. CF₃ H H H4. CF₃ H H CH₃ 5. NO₂ H H H 6. NO₂ H H CH₃ 7. CH₃ H H H 8. CH₃ H H CH₃9. NHSO₂CH₃ H H H 10. NHSO₂CH₃ H H CH₃ 11. OCH₂C₆H₅ H H H 12. OCH₂C₆H₅ HH CH₃ 13. OCH₂C₆H₄—Cl(3) H H H 14. OCH₂C₆H₄—Cl(3) H H CH₃ 15.OCH₂C₆H₄—Cl(4) H H H 16. OCH₂C₆H₄—Cl(4) H H CH₃ 17. OCH₂C₆H₄—F(3) H H H18. OCH₂C₆H₄—F(3) H H CH₃ 19. OCH₂C₆H₄—F(4) H H H 20. OCH₂C₆H₄—F(4) H HCH₃ 21. OCH₂C₆H₄—CF₃(3) H H H 22. OCH₂C₆H₄—CF₃(3) H H CH₃ 23.OCH₂C₆H₄—CF₃(4) H H H 24. OCH₂C₆H₄—CF₃(4) H H CH₃ 25. OCH₂C₆H₄—NO₂(3) HH H 26. OCH₂C₆H₄—NO₂(3) H H CH₃ 27. OCH₂C₆H₄—NO₂(4) H H H 28.OCH₂C₆H₄—NO₂(4) H H CH₃ 29. OCH₂C₆H₄—NHSO₂CH₃(3) H H H 30.OCH₂C₆H₄—NHSO₂CH₃(3) H H CH₃ 31. OCH₂C₆H₄—NHSO₂CH₃(4) H H H 32.OCH₂C₆H₄—NHSO₂CH₃(4) H H CH₃ 33. OCH₂C₆H₄—CN(3) H H H 34. OCH₂C₆H₄—CN(3)H H CH₃ 35. OCH₂C₆H₄—CN(4) H H H 36. OCH₂C₆H₄—CN(4) H H CH₃ 37.OCH₂C₆H₄—CONH₂(3) H H H 38. OCH₂C₆H₄—CONH₂(3) H H CH₃ 39.OCH₂C₆H₄—CONH₂(4) H H H 40. OCH₂C₆H₄—CONH₂(4) H H CH₃ 41.OCH₂C₆H₄—CH₂CN(3) H H H 42. OCH₂C₆H₄—CH₂CN(3) H H CH₃ 43.OCH₂C₆H₄—CH₂CN(4) H H H 44. OCH₂C₆H₄—CH₂CN(4) H H CH₃ 45.OCH₂C₆H₄—CH₂CONH₂(3) H H H 46. OCH₂C₆H₄—CH₂CONH₂(3) H H CH₃ 47.OCH₂C₆H₄—CH₂CONH₂(4) H H H 48. OCH₂C₆H₄—CH₂CONH₂(4) H H CH₃ 49.OCH₂C₆H₄—OCH₂CN(3) H H H 50. OCH₂C₆H₄—OCH₂CN(3) H H CH₃ 51.OCH₂C₆H₄—OCH₂CN(4) H H H 52. OCH₂C₆H₄—OCH₂CN(4) H H CH₃ 53.OCH₂C₆H₄—OCH₂CONH₂(3) H H H 54. OCH₂C₆H₄—OCH₂CONH₂(3) H H CH₃ 55.OCH₂C₆H₄—OCH₂CONH₂(4) H H H 56. OCH₂C₆H₄—OCH₂CONH₂(4) H H CH₃ 57.OCH₂C₆H₃—(CN)₂(3,5) H H H 58. OCH₂C₆H₃—(CN)₂(3,5) H H CH₃ 59.OCH₂C₆H₃—(CN)₂(3,5) H H H 60. OCH₂C₆H₃—(CN)₂(3,5) H H CH₃ 61.OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 62. OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃ 63.OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 64. OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃ 65.OCH₂CH₂C₆H₅ H H H 66. OCH₂CH₂C₆H₅ H H CH₃ 67. OCH₂C₆H₄C₆H₄CN(2) H H H68. OCH₂C₆H₄C₆H₄CN(2) H H CH₃ 69. OCH₂C₆H₄C₆H₄CONH₂(2) H H H 70.OCH₂C₆H₄C₆H₄CONH₂(2) H H CH₃

TABLE VIIb

Ex. # X¹ X X² R 1. OCH₂CH═CH₂ H H H 2. OCH₂CH═CH₂ H H CH₃ 3. CF₃ H H H4. CF₃ H H CH₃ 5. NO₂ H H H 6. NO₂ H H CH₃ 7. CH₃ H H H 8. CH₃ H H CH₃9. NHSO₂CH₃ H H H 10. NHSO₂CH₃ H H CH₃ 11. OCH₂C₆H₅ H H H 12. OCH₂C₆H₅ HH CH₃ 13. OCH₂C₆H₄—Cl(3) H H H 14. OCH₂C₆H₄—Cl(3) H H CH₃ 15.OCH₂C₆H₄—Cl(4) H H H 16. OCH₂C₆H₄—Cl(4) H H CH₃ 17. OCH₂C₆H₄—F(3) H H H18. OCH₂C₆H₄—F(3) H H CH₃ 19. OCH₂C₆H₄—F(4) H H H 20. OCH₂C₆H₄—F(4) H HCH₃ 21. OCH₂C₆H₄—CF₃(3) H H H 22. OCH₂C₆H₄—CF₃(3) H H CH₃ 23.OCH₂C₆H₄—CF₃(4) H H H 24. OCH₂C₆H₄—CF₃(4) H H CH₃ 25. OCH₂C₆H₄—NO₂(3) HH H 26. OCH₂C₆H₄—NO₂(3) H H CH₃ 27. OCH₂C₆H₄—NO₂(4) H H H 28.OCH₂C₆H₄—NO₂(4) H H CH₃ 29. OCH₂C₆H₄—NHSO₂CH₃(3) H H H 30.OCH₂C₆H₄—NHSO₂CH₃(3) H H CH₃ 31. OCH₂C₆H₄—NHSO₂CH₃(4) H H H 32.OCH₂C₆H₄—NHSO₂CH₃(4) H H CH₃ 33. OCH₂C₆H₄—CN(3) H H H 34. OCH₂C₆H₄—CN(3)H H CH₃ 35. OCH₂C₆H₄—CN(4) H H H 36. OCH₂C₆H₄—CN(4) H H CH₃ 37.OCH₂C₆H₄—CONH₂(3) H H H 38. OCH₂C₆H₄—CONH₂(3) H H CH₃ 39.OCH₂C₆H₄—CONH₂(4) H H H 40. OCH₂C₆H₄—CONH₂(4) H H CH₃ 41.OCH₂C₆H₄—CH₂CN(3) H H H 42. OCH₂C₆H₄—CH₂CN(3) H H CH₃ 43.OCH₂C₆H₄—CH₂CN(4) H H H 44. OCH₂C₆H₄—CH₂CN(4) H H CH₃ 45.OCH₂C₆H₄—CH₂CONH₂(3) H H H 46. OCH₂C₆H₄—CH₂CONH₂(3) H H CH₃ 47.OCH₂C₆H₄—CH₂CONH₂(4) H H H 48. OCH₂C₆H₄—CH₂CONH₂(4) H H CH₃ 49.OCH₂C₆H₄—OCH₂CN(3) H H H 50. OCH₂C₆H₄—OCH₂CN(3) H H CH₃ 51.OCH₂C₆H₄—OCH₂CN(4) H H H 52. OCH₂C₆H₄—OCH₂CN(4) H H CH₃ 53.OCH₂C₆H₄—OCH₂CONH₂(3) H H H 54. OCH₂C₆H₄—OCH₂CONH₂(3) H H CH₃ 55.OCH₂C₆H₄—OCH₂CONH₂(4) H H H 56. OCH₂C₆H₄—OCH₂CONH₂(4) H H CH₃ 57.OCH₂C₆H₃—(CN)₂(3,5) H H H 58. OCH₂C₆H₃—(CN)₂(3,5) H H CH₃ 59.OCH₂C₆H₃—(CN)₂(3,5) H H H 60. OCH₂C₆H₃—(CN)₂(3,5) H H CH₃ 61.OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 62. OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃ 63.OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 64. OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃ 65.OCH₂CH₂C₆H₅ H H H 66. OCH₂CH₂C₆H₅ H H CH₃ 67. OCH₂C₆H₄C₆H₄CN(2) H H H68. OCH₂C₆H₄C₆H₄CN(2) H H CH₃ 69. OCH₂C₆H₄C₆H₄CONH₂(2) H H H 70.OCH₂C₆H₄C₆H₄CONH₂(2) H H CH₃

TABLE VIIc

Ex. # X² X X¹ R 1. OCH₂CH═CH₂ H H H 2. OCH₂CH═CH₂ H H CH₃ 3. CF₃ H H H4. CF₃ H H CH₃ 5. NO₂ H H H 6. NO₂ H H CH₃ 7. CH₃ H H H 8. CH₃ H H CH₃9. NHSO₂CH₃ H H H 10. NHSO₂CH₃ H H CH₃ 11. OCH₂C₆H₅ H H H 12. OCH₂C₆H₅ HH CH₃ 13. OCH₂C₆H₄—Cl(3) H H H 14. OCH₂C₆H₄—Cl(3) H H CH₃ 15.OCH₂C₆H₄—Cl(4) H H H 16. OCH₂C₆H₄—Cl(4) H H CH₃ 17. OCH₂C₆H₄—F(3) H H H18. OCH₂C₆H₄—F(3) H H CH₃ 19. OCH₂C₆H₄—F(4) H H H 20. OCH₂C₆H₄—F(4) H HCH₃ 21. OCH₂C₆H₄—CF₃(3) H H H 22. OCH₂C₆H₄—CF₃(3) H H CH₃ 23.OCH₂C₆H₄—CF₃(4) H H H 24. OCH₂C₆H₄—CF₃(4) H H CH₃ 25. OCH₂C₆H₄—NO₂(3) HH H 26. OCH₂C₆H₄—NO₂(3) H H CH₃ 27. OCH₂C₆H₄—NO₂(4) H H H 28.OCH₂C₆H₄—NO₂(4) H H CH₃ 29. OCH₂C₆H₄—NHSO₂CH₃(3) H H H 30.OCH₂C₆H₄—NHSO₂CH₃(3) H H CH₃ 31. OCH₂C₆H₄—NHSO₂CH₃(4) H H H 32.OCH₂C₆H₄—NHSO₂CH₃(4) H H CH₃ 33. OCH₂C₆H₄—CN(3) H H H 34. OCH₂C₆H₄—CN(3)H H CH₃ 35. OCH₂C₆H₄—CN(4) H H H 36. OCH₂C₆H₄—CN(4) H H CH₃ 37.OCH₂C₆H₄—CONH₂(3) H H H 38. OCH₂C₆H₄—CONH₂(3) H H CH₃ 39.OCH₂C₆H₄—CONH₂(4) H H H 40. OCH₂C₆H₄—CONH₂(4) H H CH₃ 41.OCH₂C₆H₄—CH₂CN(3) H H H 42. OCH₂C₆H₄—CH₂CN(3) H H CH₃ 43.OCH₂C₆H₄—CH₂CN(4) H H H 44. OCH₂C₆H₄—CH₂CN(4) H H CH₃ 45.OCH₂C₆H₄—CH₂CONH₂(3) H H H 46. OCH₂C₆H₄—CH₂CONH₂(3) H H CH₃ 47.OCH₂C₆H₄—CH₂CONH₂(4) H H H 48. OCH₂C₆H₄—CH₂CONH₂(4) H H CH₃ 49.OCH₂C₆H₄—OCH₂CN(3) H H H 50. OCH₂C₆H₄—OCH₂CN(3) H H CH₃ 51.OCH₂C₆H₄—OCH₂CN(4) H H H 52. OCH₂C₆H₄—OCH₂CN(4) H H CH₃ 53.OCH₂C₆H₄—OCH₂CONH₂(3) H H H 54. OCH₂C₆H₄—OCH₂CONH₂(3) H H CH₃ 55.OCH₂C₆H₄—OCH₂CONH₂(4) H H H 56. OCH₂C₆H₄—OCH₂CONH₂(4) H H CH₃ 57.OCH₂C₆H₃—(CN)₂(3,5) H H H 58. OCH₂C₆H₃—(CN)₂(3,5) H H CH₃ 59.OCH₂C₆H₃—(CN)₂(3,5) H H H 60. OCH₂C₆H₃—(CN)₂(3,5) H H CH₃ 61.OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 62. OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃ 63.OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 64. OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃ 65.OCH₂CH₂C₆H₅ H H H 66. OCH₂CH₂C₆H₅ H H CH₃ 67. OCH₂C₆H₄C₆H₄CN(2) H H H68. OCH₂C₆H₄C₆H₄CN(2) H H CH₃ 69. OCH₂C₆H₄C₆H₄CONH₂(2) H H H 70.OCH₂C₆H₄C₆H₄CONH₂(2) H H CH₃

Numerous modifications and variations of the present invention arepossible in light of the above teachings. It is therefore to beunderstood that within the scope of the appended claims, the inventionmay be practiced otherwise that as specifically described herein.

What is claimed is:
 1. A method of treating a disease, comprising:administering to a mammal in need thereof a therapeutically effectiveamount of a compound of formula I or II, or a stereoisomer orpharmaceutically acceptable salt thereof, wherein the disease isselected from obesity, Type 2 diabetes, hypertension, dyslipidemia, highblood pressure, insulin resistance, and a combination thereof:

wherein: R, at each occurrence, is independently selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, and C₂₋₆ alkynyl; R¹ is selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R,CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂),_(n)PO(OR)₂; A⁻ is a counterion; V is selected from O⁻, C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl;X, X¹, X², and X³ are independently selected from H, OR, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, —CN, (CH₂)_(n)CO₂R,(CH₂)_(n)CONR₂, (CH₂)_(n)CN, O(CH₂)_(n)CN, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, SO₂NRCH₃,OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl,NR(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m),CO₂R, O(CH₂)_(n)-aryl-C₂₋₆alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂,O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)-PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-NRC₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, andNR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, wherein aryl is substituted with 1-2X⁴; X⁴ is selected from H, OR, O—C₂₋₆ alkenyl, C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl; Q is selected from H, OH, C₁₋₆ alkoxy, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl, O—C₂₋₆ alkenyl-CO₂R,OCH₂CH₂CONRCH₂CO₂R, OCH₂CHMCONRCH₂CO₂R, O(CH₂)^(n)PO(OR)₂,O(CH₂)_(n)SO₂OR, OCH₂CH(NHAc)CO₂R, OCH₂CH(NHR)CO₂R, and O(CH₂)_(n)-aryl;W is selected from H, CO₂R, CON(R)₂, CH₂OH, CH₂OC₁₋₆ alkyl, CH₂OC₂₋₆alkenyl, CH₂O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CON(R)₂, CH₂O—C₂₋₆alkenyl-CO₂R, CH₂OCH₂CH₂CONRCH₂CO₂R, CH₂OCH₂CHMCONRCH₂CO₂R,CH₂O(CH₂)^(n)PO(OR)₂, CH₂O(CH₂)_(n)SO₂OR, CH₂OCH₂CH(NHAc)CO₂R,CH₂OCH₂CH(NHR)CO₂R, CH₂O—C₂₋₆ alkenyl, and CH₂O(CH₂)_(n)CONH₂, andCH₂O(CH₂)_(n)-aryl; M is independently selected from H, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, and (CH₂)_(n)-aryl,wherein aryl is substituted with 1-2 X⁴; m is independently selectedfrom 0, 1, 2, 3, and 4; and, n is independently selected from 1, 2, 3,and 4; provided that at least one of X, X¹, X², and X³ is other than H,alkyl, alkoxy, hydroxyl, CF₃, and halo.
 2. A method of treating of claim1, wherein the compound is of formula I₁ or II₁, or a stereoisomer orpharmaceutically acceptable salt thereof:


3. A method of treating of claim 1, wherein the compound is of formulaIa, or a stereoisomer or pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H andC₁₋₄ alkyl; R¹ is selected from H and C₁₋₄ alkyl; X and X¹ areindependently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, halogen, CF₃, —CN, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃,SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, O(CH₂)_(n)-aryl,NR(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl issubstituted with 1-2 X⁴; X⁴ is selected from H, OH, C₁₋₄ alkoxy, C₁₋₄alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂,NRSO₂CH₃, and, SO₂N(R)C₁₋₆alkyl; n is independently selected from 1, 2,and 3; provided that at least one of X and X¹ is other than H, alkyl,alkoxy, hydroxyl, CF₃, and halo.
 4. A method of of claim 3, wherein: oneof X and X¹ is H and the other is selected from OH, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, —CN, C₁₋₄ alkoxy,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄alkyl)₂, CH₂-aryl, O(CH₂)_(n)-aryl, NR(CH₂)_(n)-aryl,O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂,NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, andNR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl is substituted with 1-2 X⁴;provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, CF₃, and halo.
 5. A method of treating of claim 3, wherein thecompound is of formula Ia₁, or a stereoisomer or pharmaceuticallyacceptable salt thereof:


6. A method of of claim 1, wherein the compound is of formula Ib, or astereoisomer or pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H andC₁₋₄ alkyl; R¹ is selected from H, C₁₋₄ alkyl, (CH₂)_(m)CO₂R, C₂₋₄alkenyl-CO₂R, CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂),PO(OR)₂; X andX¹ are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, halogen, CF₃, —CN, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃,SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, O(CH₂)_(n)-aryl,NR(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, NR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl issubstituted with 1-2 X⁴; X⁴ is selected from H, OH, C₁₋₄ alkoxy, C₁₋₄alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂,NRSO₂CH₃, and, SO₂N(R)C₁₋₆alkyl; W is selected from H, CH₂OH, CH₂OC₁₋₄alkyl, CH₂OC₂₋₄ alkenyl, CH₂O(CH₂)_(n)CO₂R, CH₂O—C₂₋₄ alkenyl-CO₂R,CH₂O(CH₂)_(n)CON(R)₂, CH₂O(CH₂)_(n)PO(OR)₂, and CH₂O(CH₂)_(n)-aryl; m isindependently selected from 0, 1, and 2; and, n is independentlyselected from 1, 2, and 3; provided that at least one of X and X¹ isother than H, alkyl, alkoxy, hydroxyl, CF₃, and halo.
 7. A method oftreating of claim 6, wherein: one of X and X¹ is H and the other isselected from OH, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃,—CN, C₁₋₄ alkoxy, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃, SO₂NRCH₃,CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, O(CH₂)_(n)-aryl, NR(CH₂)_(n)-aryl,O(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂,NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN,NR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl is substituted with 1-2 X⁴;provided that at least one of X and X¹ is other than H, alkyl, alkoxy,hydroxyl, CF₃, and halo.
 8. A method of treating of claim 6, wherein thecompound is of formula Ib₁, or a stereoisomer or pharmaceuticallyacceptable salt thereof:


9. A method of treating of claim 1, wherein the compound is of formulaIc, or a stereoisomer or pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H, C₁₋₄alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl; R¹ is selected from H and C₁₋₄alkyl; X, X¹, X², and X³ are independently selected from H, OR, C₁₋₄alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, —CN, (CH₂)_(n)CO₂R,(CH₂)_(n)CONR₂, (CH₂)_(n)CN, O(CH₂)_(n)CN, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, SO₂NRCH₃,OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl,O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂, O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)-PO(OR)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-NRC₂₋₄alkenyl-CO₂R,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-aryl-NR(CH₂)_(n)-PO(OR)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R,NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, andNR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, wherein is substituted with 1-2 X⁴ ;X⁴ is selected from H, OR, C₁₋₄ alkoxy, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl; A⁻ is selected from Cl and Br; M is independentlyselected from H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₂₋₄ alkenyl, C₂₋₄alkynyl, aryl, and (CH₂)_(n)-aryl; and, m is independently selected from0, 1, and 2; and, n is independently selected from 1, 2, and 3; providedthat at least one of X, X¹, X², and X³ is other than H, alkyl, alkoxy,hydroxyl, CF₃, and halo.
 10. A method of treating of claim 9, wherein:three of X, X¹, X², and X³ are H and the fourth is selected from OH,C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, C₁₋₄ alkoxy, —CN,(CH₂)_(n)CO₂R, (CH₂)_(n)CONR₂, (CH₂)_(n)CN, O(CH₂)_(n)CN,O(CH₂)_(n)CO₂R, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄ alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R,NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂,NR(CH₂)_(n)SO₂OR, SO₂NRCH₃, OCH₂CHMCONRCH₂CO₂R, CH₂-aryl,O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR, OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₄alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂,O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)-PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-NRC₂₋₄ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₄ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(n),CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-NR—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₄ alkenyl-CO₂R, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, andNR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)— wherein aryl issubstituted with 1-2 X⁴; provided that at least one of X, X¹, X², and X³is other than H, alkyl, alkoxy, hydroxyl, CF₃, and halo.
 11. A method oftreating of claim 9, wherein the compound is of formula Ic₁, or astereoisomer or pharmaceutically acceptable salt thereof:


12. A method of treating of claim 1, wherein the compound is of formulaId, or a stereoisomer or pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H, C₁₋₄alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl; R¹ is selected from H, C₁₋₄alkyl, (CH₂)_(m)CO₂R, (CH₂)_(n)PO(OR)₂, C₂₋₄ alkenyl, and C₂₋₄ alkynyl;X, X¹, and X² are independently selected from H, OR, C₁₋₄ alkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, halogen, CF₃, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl,NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄ alkyl)₂, CH₂-aryl, O(CH₂)_(n)-aryl,O(CH₂)_(n)-aryl(CH₂)_(m)CN, O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-arylO(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-biphenyl, O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂,NR(CH₂)_(n)-biphenyl, NR(CH₂)_(n)-biphenyl-CN, andNR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl is substituted with 1-2 X⁴; X⁴is selected from H, OH, C₁₋₆ alkoxy C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl; Q is selected from OH, C₁₋₄ alkoxy, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, O—C₂₋₄ alkenyl-CO₂R,OCH₂CH₂CONRCH₂CO₂R, OCH₂CHMCONRCH₂CO₂R, O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)SO₂OR, OCH₂CH(NHAc)CO₂R, OCH₂CH(NHR)CO₂R, and O(CH₂)_(n)-aryl;M is independently selected from H, C₁₋₄ alkyl, C₃₋₆ cycloalkyl, C₂₋₄alkenyl, C₂₋₄ alkynyl, aryl, and (CH₂)_(n)-aryl; and, m is independentlyselected from 0, 1, and 2; and, n is independently selected from 1, 2,and 3; provided that at least one of X, X¹, and X² is other than H,alkyl, alkoxy, hydroxyl, CF₃, and halo.
 13. A method of treating ofclaim 12, wherein: two of X, X¹, and X² are H and the third is selectedfrom OH, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, C₁₋₄alkoxy, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃, SO₂NRCH₃, CH₂N(C₁₋₄alkyl)₂, CH₂-aryl, O(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl issubstituted with 1-2 X⁴; provided that at least one of X, X¹, and X² isother than H, alkyl, alkoxy, hydroxyl, CF₃, and halo.
 14. A method oftreating of claim 12, wherein the compound is of formula Id₁, or astereoisomer or pharmaceutically acceptable salt thereof:


15. A method of treating of claim 1, wherein the compound is of formulaIIa, or a stereoisomer or pharmaceutically acceptable salt thereof:

wherein: R, at each occurrence, is independently selected from H, C₁₋₄alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl; R¹ is selected from H and C₁₋₄alkyl; A⁻ is selected from Cl⁻ and Br⁻; V is selected from O⁻, C₁₋₄alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl; X and X¹ are independentlyselected from H, OR, C₁₋₄ alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen,CF₃, O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl,O(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl issubstituted with 1-2 X⁴; X⁴ is selected from H, OR, C₁₋₆ alkoxy C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂,NRSO₂CH₃, and, SO₂N(R)C₁₋₆alkyl; n is independently selected from 1, 2,and 3; provided that at least one of X and X¹ is other than H, alkyl,alkoxy, hydroxyl, CF₃, and halo.
 16. A method of treating of claim 15,wherein: one of X and X¹ is H and the other is selected from OH, C₁₋₄alkyl, C₂₋₄ alkenyl, C₂₋₄ alkynyl, halogen, CF₃, C₁₋₄ alkoxy,O(CH₂)_(n)CON(R)₂, O—C₂₋₄ alkenyl, NRSO₂CH₃, SO₂NRCH₃, CH₂-aryl,O(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-arylO(CH₂)_(n)CN,O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl(CH₂)_(m)CN,NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-CN, O(CH₂)_(n)-biphenyl-CONH₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-CN, and NR(CH₂)_(n)-biphenyl-CONH₂, wherein aryl issubstituted with 1-2 X⁴; provided that at least one of X and X¹ is otherthan H, alkyl, alkoxy, hydroxyl, CF₃, and halo.
 17. A method of treatingof claim 15, wherein the compound is of formula IIa₁, or a stereoisomeror pharmaceutically acceptable salt thereof:


18. A method of treating a disease, comprising: administering to amammal in need thereof a therapeutically effective amount of a compoundof formula I or II or a pharmaceutically acceptable salt form thereof,wherein the disease is a co-morbidty of obesity selected from Type 2diabetes, Metabolic Syndrome, dementia, hypertension, pulmonaryhypoventilation syndrome, coronary artery disease, arterial scleroticdisease, and high cholesterol:

wherein: R, at each occurrence, is independently selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, and C₂₋₆ alkynyl; R¹ is selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R,CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂; A⁻ is a counterion; V is selected from O⁻, C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl;X, X¹, X², and X³ are independently selected from H, OR, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, —CN, (CH₂)_(n)CO₂R,(CH₂)_(n)CONR₂, (CH₂)_(n)CN, O(CH₂)_(n)CN, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, SO₂NRCH₃,OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl,NR(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₆alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂,O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)-PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-NRC₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, andNR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, wherein aryl is substituted with 1-2X⁴; X⁴ is selected from H, OR, O—C₂₋₆ alkenyl, C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl; Q is selected from H, OH, C₁₋₆ alkoxy, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl, O—C₂₋₆ alkenyl-CO₂R,OCH₂CH₂CONRCH₂CO₂R, OCH₂CHMCONRCH₂CO₂R, O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)SO₂OR, OCH₂CH(NHAc)CO₂R, OCH₂CH(NHR)CO₂R, and O(CH₂)_(n)-aryl;W is selected from H, CO₂R, CON(R)₂, CH₂OH, CH₂OC₁₋₆ alkyl, CH₂OC₂₋₆alkenyl, CH₂O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CON(R)₂, CH₂O—C₂₋₆alkenyl-CO₂R, CH₂OCH₂CH₂CONRCH₂CO₂R, CH₂OCH₂CHMCONRCH₂CO₂R,CH₂O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)SO₂OR, CH₂OCH₂CH(NHAc)CO₂R,CH₂OCH₂CH(NHR)CO₂R, CH₂O—C₂₋₆ alkenyl, and CH₂O(CH₂)_(n)CONH₂, andCH₂O(CH₂)_(n)-aryl; M is independently selected from H, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, and (CH₂)_(n)-aryl,wherein aryl is substituted with 1-2 X⁴; m is independently selectedfrom 0, 1, 2, 3, and 4; and, n is independently selected from 1, 2, 3,and 4; provided that at least one of X, X¹, X², and X³ is other than H,alkyl, alkoxy, hydroxyl, CF₃, and halo.
 19. A method of treating adisease, comprising: administering to a mammal in need thereof atherapeutically effective amount of a compound of formula I or II or apharmaceutically acceptable salt form thereof, wherein the disease is aCNS disorder selected from Parkinson's disease, depression, anxiety,panic attack, social phobia, schizophrenia, anorexia, and neuropathicpain:

wherein: R, at each occurrence, is independently selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, and C₂₋₆ alkynyl; R¹ is selected from H, C₁₋₆alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, (CH₂)_(m)CO₂R, C₂₋₆ alkenyl-CO₂R,CH₂CH(NHAc)CO₂R, CH₂CH(NHR)CO₂R, and, (CH₂)_(n)PO(OR)₂; A⁻ is a counterion; V is selected from O⁻, C₁₋₄ alkyl, C₂₋₄ alkenyl, and C₂₋₄ alkynyl;X, X¹, X², and X³ are independently selected from H, OR, C₁₋₆ alkyl,C₂₋₆ alkenyl, C₂₋₆ alkynyl, halogen, CF₃, —CN, (CH₂)_(n)CO₂R,(CH₂)_(n)CONR₂, (CH₂)_(n)CN, O(CH₂)_(n)CN, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)PO(OR)₂, NR—C₂₋₄alkenyl, NRSO₂CH₃, NR(CH₂)_(n)CO₂R, NR(CH₂)_(n)CON(R)₂, NR—C₂₋₄alkenyl-CO₂R, NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)SO₂OR, SO₂NRCH₃,OCH₂CHMCONRCH₂CO₂R, CH₂-aryl, O(CH₂)_(n)PO(OR)₂, O(CH₂)_(n)SO₂OR,OCH₂(CH₂)_(n)N⁺(CH₃)₃A⁻, O(CH₂)_(n)-biphenyl,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, O(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,O(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, NR(CH₂)_(n)-biphenyl,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CO₂R, NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CN,NR(CH₂)_(n)-biphenyl-(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl,NR(CH₂)_(n)-aryl, O(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, O(CH₂)_(n)-aryl-C₂₋₆alkenyl-CO₂R, O(CH₂)_(n)-aryl(CH₂)_(m)CN,O(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂, O(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂,O(CH₂)_(n)-aryl-O(CH₂)_(n)CO₂R, O(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R,O(CH₂)_(n)-arylO(CH₂)_(n)CN, O(CH₂)_(n)-arylO(CH₂)_(n)CON(R)₂,O(CH₂)_(n)-arylO(CH₂)_(n)-PO(OR)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,O(CH₂)_(n)-aryl-NRC₂₋₆ alkenyl-CO₂R, O(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,O(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂, O(CH₂)_(n)-aryl-NR(CH₂)_(n)-PO(OR)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)CO₂R, NR(CH₂)_(n)-aryl-C₂₋₆ alkenyl-CO₂R,NR(CH₂)_(n)-aryl(CH₂)_(m)CN, NR(CH₂)_(n)-aryl(CH₂)_(m)CON(R)₂,NR(CH₂)_(n)-aryl(CH₂)_(m)-PO(OR)₂, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-NR—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)CON(R)₂,NR(CH₂)_(n)-aryl-NR(CH₂)_(n)PO(OR)₂, NR(CH₂)_(n)-arylO(CH₂)_(n)CO₂R,NR(CH₂)_(n)-aryl-O—C₂₋₆ alkenyl-CO₂R, NR(CH₂)_(n)-arylO(CH₂)_(n)CN,NR(CH₂)_(n)-aryl-O(CH₂)_(n)CON(R)₂, andNR(CH₂)_(n)-arylO(CH₂)_(n)PO(OR)₂, wherein aryl is substituted with 1-2X⁴; X⁴ is selected from H, OR, O—C₂₋₆ alkenyl, C₁₋₆ alkyl, C₂₋₆ alkenyl,C₂₋₆ alkynyl, halogen, CF₃, nitro, —CN, C(O)NR₂, NRSO₂CH₃, and,SO₂N(R)C₁₋₆alkyl; Q is selected from H, OH, C₁₋₆ alkoxy, O(CH₂)_(n)CO₂R,O(CH₂)_(n)CON(R)₂, O—C₂₋₆ alkenyl, O-C₂₋₆ alkenyl-CO₂R,OCH₂CH₂CONRCH₂CO₂R, OCH₂CHMCONRCH₂CO₂R, O(CH₂)_(n)PO(OR)₂,O(CH₂)_(n)SO₂OR, OCH₂CH(NHAc)CO₂R, OCH₂CH(NHR)CO₂R, and O(CH₂)_(n)-aryl;W is selected from H, CO₂R, CON(R)₂, CH₂OH, CH₂OC₁₋₆ alkyl, CH₂OC₂₋₆alkenyl, CH₂O(CH₂)_(n)CO₂R, CH₂O(CH₂)_(n)CON(R)₂, CH₂O—C₂₋₆alkenyl-CO₂R, CH₂OCH₂CH₂CONRCH₂CO₂R, CH₂OCH₂CHMCONRCH₂CO₂R,CH₂O(CH₂)_(n)PO(OR)₂, CH₂O(CH₂)_(n)SO₂OR, CH₂OCH₂CH(NHAc)CO₂R,CH₂OCH₂CH(NHR)CO₂R, CH₂O—C₂₋₆ alkenyl, and CH₂O(CH₂)_(n)CONH₂, andCH₂O(CH₂)_(n)-aryl; M is independently selected from H, C₁₋₆ alkyl, C₃₋₈cycloalkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, aryl, and (CH₂)_(n)-aryl,wherein aryl is substituted with 1-2 X⁴; m is independently selectedfrom 0, 1, 2, 3, and 4; and, n is independently selected from 1, 2, 3,and 4; provided that at least one of X, X¹, X², and X³ is other than H,alkyl, alkoxy, hydroxyl, CF₃, and halo.
 20. The method of claim 1,wherein the compound is a compound selected from Tables A-C or astereoisomer or pharmaceutically acceptable salt thereof: TABLE A

All compounds racemic Number X R 1 CH₂C₆H₅ H 2 CH₂CH₂C₆H₅ H 3 CH₂CO₂EtCH₃ 4 CH₂CO₂Et H

TABLE B

All compounds racemic Number X R 5 CH₂C₆H₅ H 6 CH₂CH₂C₆H₅ H 7 CH₂C₆H₅CH₃ 8 CH₂CO₂Et H 9 CH₂CO₂Et CH₃ 10 CH₂CO₂H CH₃ 11 (CH₂)₄CO₂Et H 12CH₂CH═CHCO₂Et CH₃ 13 CH₂CH═CHCO₂Et H 14 CH₂C₆H₅CO₂Me(4) CH₃ 15CH₂C₆H₅CO₂Me(4) H 16 CH₂C₆H₅CONH₂(4) H 17 CH₂C₆H₅CO₂Me(3) CH₃ 18CH₂C₆H₅CO₂Me(3) H 19 CH₂C₆H₅CO₂H(3) H 20 CH₂C₆H₅CONH₂(3) H 21CH₂C₆H₅CH₂CO₂Me(4) H 22 CH₂C₆H₅CH₂CO₂H(4) H 23 CH₂C₆H₅OCH₂CO₂Et(4) H 24CH₂C₆H₅OCH₂CONH₂(4) H 26 CH₂CH₂CH₂PO(OEt)₂ H

TABLE C

All compounds racemic Number X R 27 CH₂C₆H₅ H 28 CH₂C₆H₅ CH₃ 29CH₂CH₂C₆H₅ H 30 CH₂CO₂Et CH₃ 31 CH₂CH═CHCO₂Et CH₃ 32 CH₂CH═CHCO₂Et H 33CH₂C₆H₅CO₂Me(4) CH₃ 34 CH₂C₆H₅CO₂Me(4) H 35 CH₂C₆H₅CO₂Me(3) H 36CH₂C₆H₅OCH₂CN(3) H 37 CH₂C₆H₅CN(3) H 38 CH₂C₆H₅CONH₂(3) H


21. The method of claim 1, wherein the compound is a compound selectedfrom Tables I-Vb and VIIa-VIIc or a stereoisomer or a pharmaceuticallyacceptable salt thereof: TABLE I

Ex. # X X¹ R R¹ 21 OCH₂C₆H₅ H CH₃ H 22 OCH₂C₆H₅ H H H 23 OCH₂C₆H₅ H CH₃CH₃ 24 OCH₂C₆H₅ H H CH₃ 25 H OCH₂C₆H₅ CH₃ H 26 H OCH₂C₆H₅ H H 27 HOCH₂C₆H₅ CH₃ CH₃ 28 H OCH₂C₆H₅ H CH₃ 29 OCH₂C₆H₅ H CH₃ H 30 OCH₂C₆H₅ H HH 31 OCH₂C₆H₅ H CH₃ CH₃ 32 OCH₂C₆H₅ H H CH₃ 33 OCH₂CH₂C₆H₅ H CH₃ H 34OCH₂CH₂C₆H₅ H H H 35 OCH₂CH₂C₆H₅ H CH₃ CH₃ 36 OCH₂CH₂C₆H₅ H H CH₃ 37 HOCH₂CH₂C₆H₅ CH₃ H 38 H OCH₂CH₂C₆H₅ H H 39 H OCH₂CH₂C₆H₅ CH₃ CH₃ 40 HOCH₂CH₂C₆H₅ H CH₃ 41 OCH₂CH═CH₂ H CH₃ H 42 OCH₂CH═CH₂ H H H 43OCH₂CH═CH₂ H CH₃ CH₃ 44 OCH₂CH═CH₂ H H CH₃ 45 H OCH₂CH═CH₂ CH₃ H 46 HOCH₂CH═CH₂ H H 47 H OCH₂CH═CH₂ CH₃ CH₃ 48 H OCH₂CH═CH₂ H CH₃ 49OCH₂CONH₂ H CH₃ H 50 OCH₂CONH₂ H H H 51 OCH₂CONH₂ H CH₃ CH₃ 52 OCH₂CONH₂H H CH₃ 53 H OCH₂CONH₂ CH₃ H 54 H OCH₂CONH₂ H H 55 H OCH₂CONH₂ CH₃ CH₃56 H OCH₂CONH₂ H CH₃ 69 NH₂ H CH₃ H 70 NH₂ H H H 71 NH₂ H CH₃ CH₃ 72 NH₂H H CH₃ 73 NHSO₂CH₃ H CH₃ H 74 NHSO₂CH₃ H H H 75 NHSO₂CH₃ H CH₃ CH₃ 76NHSO₂CH₃ H H CH₃

TABLE IIa

Ex. # X X¹ R¹
 1. OCH₂CH═CH₂ H CO₂CH₂CH₃
 2. OCH₂CH═CH₂ H CO₂H
 3. OCH₂C₆H₅H CO₂CH₂CH₃
 4. OCH₂C₆H₅ H CO₂H
 5. OCH₂CH₂C₆H₅ H CO₂CH₂CH₃
 6. OCH₂CH₂C₆H₅H CO₂H
 7. OCH₂CONH₂ H CO₂CH₂CH₃
 8. OCH₂CONH₂ H CO₂H
 9. NH₂ H CO₂CH₂CH₃10. NH₂ H CO₂H
 11. NHSO₂CH₃ H CO₂CH₂CH₃
 12. NHSO₂CH₃ H CO₂H
 13. HOCH₂CH═CH₂ CO₂CH₂CH₃
 14. H OCH₂CH═CH₂ CO₂H
 15. H OCH₂C₆H₅ CO₂CH₂CH₃ 16.H OCH₂C₆H₅ CO₂H
 17. H OCH₂CH₂C₆H₅ CO₂CH₂CH₃
 18. H OCH₂CH₂C₆H₅ CO₂H
 19. HOCH₂CONH₂ CO₂CH₂CH₃
 20. H OCH₂CONH₂ CO₂H
 21. OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃22. OCH₂CH═CH₂ H CH₂CO₂H
 23. OCH₂C₆H₅ H CH₂CO₂CH₂CH₃
 24. OCH₂C₆H₅ HCH₂CO₂H
 25. OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃
 26. OCH₂CH₂C₆H₅ H CH₂CO₂H 27.OCH₂CONH₂ H CH₂CO₂CH₂CH₃
 28. OCH₂CONH₂ H CH₂CO₂H
 29. NH₂ H CH₂CO₂CH₂CH₃30. NH₂ H CH₂CO₂H
 31. NHSO₂CH₃ H CH₂CO₂CH₂CH₃
 32. NHSO₂CH₃ H CH₂CO₂H 33.H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃
 34. H OCH₂CH═CH₂ CH₂CO₂H
 35. H OCH₂C₆H₅CH₂CO₂CH₂CH₃
 36. H OCH₂C₆H₅ CH₂CO₂H
 37. H OCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₃
 38. HOCH₂CH₂C₆H₅ CH₂CO₂H
 39. H OCH₂CONH₂ CH₂CO₂CH₂CH₃
 40. H OCH₂CONH₂ CH₂CO₂H41. OCH₂CH═CH₂ H CH₂CO₂CH₂CH₂CH₃
 42. OCH₂CH═CH₂ H CH₂CH₂CO₂H 43.OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃
 44. OCH₂C₆H₅ H CH₂CH₂CO₂H
 45. OCH₂CH₂C₆H₅ HCH₂CO₂CH₂CH₂CH₃
 46. OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H
 47. OCH₂CONH₂ HCH₂CH₂CO₂CH₂CH₃
 48. OCH₂CONH₂ H CH₂CH₂CO₂H
 49. NH₂ H CH₂CO₂CH₂CH₂CH₃ 50.NH₂ H CH₂CH₂CO₂H
 51. NHSO₂CH₃ H CH₂CH₂CO₂CH₂CH₃
 52. NHSO₂CH₃ HCH₂CH₂CO₂H
 53. H OCH₂CH═CH₂ CH₂CO₂CH₂CH₂CH₃
 54. H OCH₂CH═CH₂ CH₂CH₂CO₂H55. H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃
 56. H OCH₂C₆H₅ CH₂CH₂CO₂H
 57. HOCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₂CH₃
 58. H OCH₂CH₂C₆H₅ CH₂CH₂CO₂H
 59. H OCH₂CONH₂CH₂CH₂CO₂CH₂CH₃
 60. H OCH₂CONH₂ CH₂CH₂CO₂H
 61. OCH₂CH═CH₂ HCH₂CH₂PO(OCH₂CH₃)₂
 62. OCH₂CH═CH₂ H CH₂CH₂PO(OH)₂
 63. OCH₂C₆H₅ HCH₂CH₂PO(OCH₂CH₃)₂
 64. OCH₂C₆H₅ H CH₂CH₂PO(OH)₂
 65. OCH₂CH₂C₆H₅ HCH₂CH₂PO(OCH₂CH₃)₂
 66. OCH₂CH₂C₆H₅ H CH₂CH₂PO(OH)₂
 67. OCH₂CONH₂ HCH₂CH₂PO(OCH₂CH₃)₂
 68. OCH₂CONH₂ H CH₂CH₂PO(OH)₂
 69. NH₂ HCH₂CH₂PO(OCH₂CH₃)₂
 70. NH₂ H CH₂CH₂PO(OH)₂
 71. NHSO₂CH₃ HCH₂CH₂PO(OCH₂CH₃)₂
 72. NHSO₂CH₃ H CH₂CH₂PO(OH)₂
 73. H OCH₂CH═CH₂CH₂CH₂PO(OCH₂CH₃)₂
 74. H OCH₂CH═CH₂ CH₂CH₂PO(OH)₂
 75. H OCH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂
 76. H OCH₂C₆H₅ CH₂CH₂PO(OH)₂
 77. H OCH₂CH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂
 78. H OCH₂CH₂C₆H₅ CH₂CH₂PO(OH)₂
 79. H OCH₂CONH₂CH₂CH₂PO(OCH₂CH₃)₂
 80. H OCH₂CONH₂ CH₂CH₂PO(OH)₂
 81. OCH₂CH═CH₂ HCH₂CH═CHCO₂CH₂CH₃
 82. OCH₂CH═CH₂ H CH₂CH═CHCO₂H
 83. OCH₂C₆H₅ HCH₂CH═CHCO₂CH₂CH₃
 84. OCH₂C₆H₅ H CH₂CH═CHCO₂H
 85. OCH₂CH₂C₆H₅ HCH₂CH═CHCO₂CH₂CH₃
 86. OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂H
 87. OCH₂CONH₂ HCH₂CH═CHCO₂CH₂CH₃
 88. OCH₂CONH₂ H CH₂CH═CHCO₂H
 89. NH₂ HCH₂CH═CHCO₂CH₂CH₃
 90. NH₂ H CH₂CH═CHCO₂H
 91. NHSO₂CH₃ HCH₂CH═CHCO₂CH₂CH₃
 92. NHSO₂CH₃ H CH₂CH═CHCO₂H
 93. H OCH₂CH═CH₂CH₂CH═CHCO₂CH₂CH₃
 94. H OCH₂CH═CH₂ CH₂CH═CHCO₂H
 95. H OCH₂C₆H₅CH₂CH═CHCO₂CH₂CH₃
 96. H OCH₂C₆H₅ CH₂CH═CHCO₂H
 97. H OCH₂CH₂C₆H₅CH₂CH═CHCO₂CH₂CH₃
 98. H OCH₂CH₂C₆H₅ CH₂CH═CHCO₂H
 99. H OCH₂CONH₂CH₂CH═CHCO₂CH₂CH₃
 100. H OCH₂CONH₂ CH₂CH═CHCO₂H

TABLE IIb

EX. # X X¹ R¹
 1. OCH₂CH═CH₂ H CO₂CH₂CH₃
 2. OCH₂CH═CH₂ H CO₂H
 3. OCH₂C₆H₅H CO₂CH₂CH₃
 4. OCH₂C₆H₅ H CO₂H
 5. OCH₂CH₂C₆H₅ H CO₂CH₂CH₃
 6. OCH₂CH₂C₆H₅H CO₂H
 7. OCH₂CONH₂ H CO₂CH₂CH₃
 8. OCH₂CONH₂ H CO₂H
 9. NH₂ H CO₂CH₂CH₃10. NH₂ H CO₂H
 11. NHSO₂CH₃ H CO₂CH₂CH₃
 12. NHSO₂CH₃ H CO₂H
 13. HOCH₂CH═CH₂ CO₂CH₂CH₃
 14. H OCH₂CH═CH₂ CO₂H
 15. H OCH₂C₆H₅ CO₂CH₂CH₃ 16.H OCH₂C₆H₅ CO₂H
 17. H OCH₂CH₂C₆H₅ CO₂CH₂CH₃
 18. H OCH₂CH₂C₆H₅ CO₂H
 19. HOCH₂CONH₂ CO₂CH₂CH₃
 20. H OCH₂CONH₂ CO₂H
 21. OCH₂CH═CH₂ H CH₂CO₂CH₂CH₃22. OCH₂CH═CH₂ H CH₂CO₂H
 23. OCH₂C₆H₅ H CH₂CO₂CH₂CH₃
 24. OCH₂C₆H₅ HCH₂CO₂H
 25. OCH₂CH₂C₆H₅ H CH₂CO₂CH₂CH₃
 26. OCH₂CH₂C₆H₅ H CH₂CO₂H 27.OCH₂CONH₂ H CH₂CO₂CH₂CH₃
 28. OCH₂CONH₂ H CH₂CO₂H
 29. NH₂ H CH₂CO₂CH₂CH₃30. NH₂ H CH₂CO₂H
 31. NHSO₂CH₃ H CH₂CO₂CH₂CH₃
 32. NHSO₂CH₃ H CH₂CO₂H 33.H OCH₂CH═CH₂ CH₂CO₂CH₂CH₃
 34. H OCH₂CH═CH₂ CH₂CO₂H
 35. H OCH₂C₆H₅CH₂CO₂CH₂CH₃
 36. H OCH₂C₆H₅ CH₂CO₂H
 37. H OCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₃
 38. HOCH₂CH₂C₆H₅ CH₂CO₂H
 39. H OCH₂CONH₂ CH₂CO₂CH₂CH₃
 40. H OCH₂CONH₂ CH₂CO₂H41. OCH₂CH═CH₂ H CH₂CO₂CH₂CH₂CH₃
 42. OCH₂CH═CH₂ H CH₂CH₂CO₂H 43.OCH₂C₆H₅ H CH₂CH₂CO₂CH₂CH₃
 44. OCH₂C₆H₅ H CH₂CH₂CO₂H
 45. OCH₂CH₂C₆H₅ HCH₂CO₂CH₂CH₂CH₃
 46. OCH₂CH₂C₆H₅ H CH₂CH₂CO₂H
 47. OCH₂CONH₂ HCH₂CH₂CO₂CH₂CH₃
 48. OCH₂CONH₂ H CH₂CH₂CO₂H
 49. NH₂ H CH₂CO₂CH₂CH₂CH₃ 50.NH₂ H CH₂CH₂CO₂H
 51. NHSO₂CH₃ H CH₂CH₂CO₂CH₂CH₃
 52. NHSO₂CH₃ HCH₂CH₂CO₂H
 53. H OCH₂CH═CH₂ CH₂CO₂CH₂CH₂CH₃
 54. H OCH₂CH═CH₂ CH₂CH₂CO₂H55. H OCH₂C₆H₅ CH₂CH₂CO₂CH₂CH₃
 56. H OCH₂C₆H₅ CH₂CH₂CO₂H
 57. HOCH₂CH₂C₆H₅ CH₂CO₂CH₂CH₂CH₃
 58. H OCH₂CH₂C₆H₅ CH₂CH₂CO₂H
 59. H OCH₂CONH₂CH₂CH₂CO₂CH₂CH₃
 60. H OCH₂CONH₂ CH₂CH₂CO₂H
 61. OCH₂CH═CH₂ HCH₂CH₂PO(OCH₂CH₃)₂
 62. OCH₂CH═CH₂ H CH₂CH₂PO(OH)₂
 63. OCH₂C₆H₅ HCH₂CH₂PO(OCH₂CH₃)₂
 64. OCH₂C₆H₅ H CH₂CH₂PO(OH)₂
 65. OCH₂CH₂C₆H₅ HCH₂CH₂PO(OCH₂CH₃)₂
 66. OCH₂CH₂C₆H₅ H CH₂CH₂PO(OH)₂
 67. OCH₂CONH₂ HCH₂CH₂PO(OCH₂CH₃)₂
 68. OCH₂CONH₂ H CH₂CH₂PO(OH)₂
 69. NH₂ HCH₂CH₂PO(OCH₂CH₃)₂
 70. NH₂ H CH₂CH₂PO(OH)₂
 71. NHSO₂CH₃ HCH₂CH₂PO(OCH₂CH₃)₂
 72. NHSO₂CH₃ H CH₂CH₂PO(OH)₂
 73. H OCH₂CH═CH₂CH₂CH₂PO(OCH₂CH₃)₂
 74. H OCH₂CH═CH₂ CH₂CH₂PO(OH)₂
 75. H OCH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂
 76. H OCH₂C₆H₅ CH₂CH₂PO(OH)₂
 77. H OCH₂CH₂C₆H₅CH₂CH₂PO(OCH₂CH₃)₂
 78. H OCH₂CH₂C₆H₅ CH₂CH₂PO(OH)₂
 79. H OCH₂CONH₂CH₂CH₂PO(OCH₂CH₃)₂
 80. H OCH₂CONH₂ CH₂CH₂PO(OH)₂
 81. OCH₂CH═CH₂ HCH₂CH═CHCO₂CH₂CH₃
 82. OCH₂CH═CH₂ H CH₂CH═CHCO₂H
 83. OCH₂C₆H₅ HCH₂CH═CHCO₂CH₂CH₃
 84. OCH₂C₆H₅ H CH₂CH═CHCO₂H
 85. OCH₂CH₂C₆H₅ HCH₂CH═CHCO₂CH₂CH₃
 86. OCH₂CH₂C₆H₅ H CH₂CH═CHCO₂H
 87. OCH₂CONH₂ HCH₂CH═CHCO₂CH₂CH₃
 88. OCH₂CONH₂ H CH₂CH═CHCO₂H
 89. NH₂ HCH₂CH═CHCO₂CH₂CH₃
 90. NH₂ H CH₂CH═CHCO₂H
 91. NHSO₂CH₃ HCH₂CH═CHCO₂CH₂CH₃
 92. NHSO₂CH₃ H CH₂CH═CHCO₂H
 93. H OCH₂CH═CH₂CH₂CH═CHCO₂CH₂CH₃
 94. H OCH₂CH═CH₂ CH₂CH═CHCO₂H
 95. H OCH₂C₆H₅CH₂CH═CHCO₂CH₂CH₃
 96. H OCH₂C₆H₅ CH₂CH═CHCO₂H
 97. H OCH₂CH₂C₆H₅CH₂CH═CHCO₂CH₂CH₃
 98. H OCH₂CH₂C₆H₅ CH₂CH═CHCO₂H
 99. H OCH₂CONH₂CH₂CH═CHCO₂CH₂CH₃
 100. H OCH₂CONH₂ CH₂CH═CHCO₂H

TABLE III

Ex. # X X¹ R¹ R″
 1. OCH₂CH═CH₂ H H CH₂—CO₂CH₂CH₃
 2. OCH₂CH═CH₂ H CH₃CH₂—CO₂H
 3. OCH₂C₆H₅ H H CH₂—CO₂CH₂CH₃
 4. OCH₂C₆H₅ H CH₃ CH₂—CO₂H 5.OCH₂CH₂C₆H₅ H H CH₂—CO₂CH₂CH₃
 6. OCH₂CH₂C₆H₅ H CH₃ CH₂—CO₂H 7.OCH₂—CONH₂ H H CH₂—CO₂CH₂CH₃
 8. OCH₂—CONH₂ H CH₃ CH₂—CO₂H
 9. NH₂ H HCH₂—CO₂CH₂CH₃
 10. NH₂ H CH₃ CH₂—CO₂H
 11. NHSO₂CH₃ H H CH₂—CO₂CH₂CH₃ 12.NHSO₂CH₃ H CH₃ CH₂—CO₂H
 13. H OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃
 14. HOCH₂CH═CH₂ CH₃ CH₂—CO₂H
 15. H OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃
 16. H OCH₂C₆H₅CH₃ CH₂—CO₂H
 17. H OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃
 18. H OCH₂CH₂C₆H₅ CH₃CH₂—CO₂H
 19. H OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃
 20. H OCH₂—CONH₂ CH₃ CH₂—CO₂H21. OCH₂CH═CH₂ H H CH₂CH₂—CO₂CH₂CH₃
 22. OCH₂CH═CH₂ H CH₃ CH₂CH₂—CO₂H 23.OCH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃
 24. OCH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H 25.OCH₂CH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃
 26. OCH₂CH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H 27.OCH₂—CONH₂ H H CH₂CH₂—CO₂CH₂CH₃
 28. OCH₂—CONH₂ H CH₃ CH₂CH₂—CO₂H
 35. NH₂H H CH₂CH₂—CO₂CH₂CH₃
 36. NH₂ H CH₃ CH₂CH₂—CO₂H
 37. NHSO₂CH₃ H HCH₂CH₂—CO₂CH₂CH₃
 38. NHSO₂CH₃ H CH₃ CH₂CH₂—CO₂H
 39. H OCH₂CH═CH₂ HCH₂CH₂—CO₂CH₂CH₃
 40. H OCH₂CH═CH₂ CH₃ CH₂CH₂—CO₂H
 41. H OCH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃
 42. H OCH₂C₆H₅ CH₃ CH₂CH₂—CO₂H
 43. H OCH₂CH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃
 44. H OCH₂CH₂C₆H₅ CH₃ CH₂CH₂—CO₂H
 45. H OCH₂—CONH₂ HCH₂CH₂—CO₂CH₂CH₃
 46. H OCH₂—CONH₂ CH₃ CH₂CH₂—CO₂H
 47. OCH₂CH═CH₂ H HCH₂CH₂P—O(OCH₂CH₃)₂
 48. OCH₂CH═CH₂ H CH₃ CH₂CH₂P—O (OH)₂
 49. OCH₂C₆H₅ HH CH₂CH₂P—O(OCH₂CH₃)₂
 50. OCH₂C₆H₅ H CH₃ CH₂CH₂P—O(OH)₂
 51. OCH₂CH₂C₆H₅H H CH₂CH₂P—O(OCH₂CH₃)₂
 52. OCH₂CH₂C₆H₅ H CH₃ CH₂CH₂P—O(OH)₂ 53.OCH₂—CONH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂
 54. OCH₂—CONH₂ H CH₃ CH₂CH₂P—O(OH)₂55. NH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂
 56. NH₂ H CH₃ CH₂CH₂P—O(OH)₂ 57.NHSO₂CH₃ H H CH₂CH₂P—O(OCH₂CH₃)₂
 58. NHSO₂CH₃ H CH₃ CH₂CH₂P—O(OH)₂
 59. HOCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂
 60. H OCH₂CH═CH₂ CH₃ CH₂CH₂P—O(OH)₂ 61.H OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂
 62. H OCH₂C₆H₅ CH₃ CH₂CH₂P—O(OH)₂
 63. HOCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂
 64. H OCH₂CH₂C₆H₅ CH₃ CH₂CH₂P—O(OH)₂65. H OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂
 66. H OCH₂—CONH₂ CH₃CH₂CH₂P—O(OH)₂
 67. OCH₂CH═CH₂ H H CH₂CH═CH—CO₂CH₂CH₃
 68. OCH₂CH═CH₂ HCH₃ CH₂CH═CH—CO₂H
 69. OCH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃
 70. OCH₂C₆H₅ H CH₃CH₂CH═CH—CO₂H
 71. OCH₂CH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃
 72. OCH₂CH₂C₆H₅ HCH₃ CH₂CH═CH—CO₂H
 73. OCH₂—CONH₂ H H CH₂CH═CH—CO₂CH₂CH₃
 74. OCH₂—CONH₂ HCH₃ CH₂CH═CH—CO₂H
 75. NH₂ H H CH₂CH═CH—CO₂CH₂CH₃
 76. NH₂ H CH₃CH₂CH═CH—CO₂H
 77. NHSO₂CH₃ H H CH₂CH═CH—CO₂CH₂CH₃
 78. NHSO₂CH₃ H CH₃CH₂CH═CH—CO₂H
 79. H OCH₂CH═CH₂ H CH₂CH═CH—CO₂CH₂CH₃
 80. H OCH₂CH═CH₂ CH₃CH₂CH═CH—CO₂H
 81. H OCH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃
 82. H OCH₂C₆H₅ CH₃CH₂CH═CH—CO₂H
 83. H OCH₂CH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃
 84. H OCH₂CH₂C₆H₅CH₃ CH₂CH═CH—CO₂H
 85. H OCH₂—CONH₂ H CH₂CH═CH—CO₂CH₂CH₃
 86. H OCH₂—CONH₂CH₃ CH₂CH═CH—CO₂H
 87. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₃
 88. OCH₂CH═CH₂ HCH₂—CO₂H CH₃
 89. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃
 90. OCH₂C₆H₅ H CH₂—CO₂HCH₃
 91. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃
 92. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₃93. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₃
 94. OCH₂—CONH₂ H CH₂—CO₂H CH₃
 95. NH₂H CH₂—CO₂CH₂CH₃ CH₃
 96. NH₂ H CH₂—CO₂H CH₃
 97. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃CH₃
 98. NHSO₂CH₃ H CH₂—CO₂H CH₃
 99. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₃ 100.H OCH₂CH═CH₂ CH₂—CO₂H CH₃
 101. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₃
 102. HOCH₂C₆H₅ CH₂—CO₂H CH₃
 103. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₃
 104. HOCH₂CH₂C₆H₅ CH₂—CO₂H CH₃
 105. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₃
 106. HOCH₂—CONH₂ CH₂—CO₂H CH₃
 107. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 108.OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₃
 109. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃110. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₃
 111. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 112. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₃ 113.OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 114. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂CH₃
 115. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 116. NH₂ H CH₂CH₂P—O(OH)₂ CH₃117. NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 118. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂CH₃
 119. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 120. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₃
 121. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 122. HOCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₃
 123. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃124. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₃
 125. H OCH₂—CONH₂CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 126. H OCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₃ 127.OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 128. OCH₂CH═CH₂ H CH₂—CO₂HCH₂CH═CH₂
 129. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 130. OCH₂C₆H₅ HCH₂—CO₂H CH₂CH═CH₂
 131. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 132.OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂CH═CH₂
 133. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃CH₂CH═CH₂
 134. OCH₂—CONH₂ H CH₂—CO₂H CH₂CH═CH₂
 135. NH₂ H CH₂—CO₂CH₂CH₃CH₂CH═CH₂
 136. NH₂ H CH₂—CO₂H CH₂CH═CH₂
 137. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃CH₂CH═CH₂
 138. NHSO₂CH₃ H CH₂—CO₂H CH₂CH═CH₂
 139. H OCH₂CH═CH₂CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 140. H OCH₂CH═CH₂ CH₂—CO₂H CH₂CH═CH₂
 141. HOCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 142. H OCH₂C₆H₅ CH₂—CO₂H CH₂CH═CH₂ 143.H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 144. H OCH₂CH₂C₆H₅ CH₂—CO₂HCH₂CH═CH₂
 145. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 146. H OCH₂—CONH₂CH₂—CO₂H CH₂CH═CH₂
 147. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂ 148.OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 149. OCH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 150. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂151. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 152. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 153. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂154. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 155. NH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 156. NH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 157.NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 158. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂CH₂CH═CH₂
 159. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 160. HOCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 161. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂
 162. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 163. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 164. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂CH═CH₂
 165. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 166. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 167. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃CH₂—CONH₂
 168. OCH₂CH═CH₂ H CH₂—CO₂H CH₂—CONH₂
 169. OCH₂C₆H₅ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂
 170. OCH₂C₆H₅ H CH₂—CO₂H CH₂—CONH₂ 171.OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 172. OCH₂CH₂C₆H₅ H CH₂—CO₂HCH₂—CONH₂
 173. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 174. OCH₂—CONH₂ HCH₂—CO₂H CH₂—CONH₂
 175. NH₂ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 176. NH₂ HCH₂—CO₂H CH₂—CONH₂
 177. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 178. NHSO₂CH₃H CH₂—CO₂H CH₂—CONH₂
 179. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 180. HOCH₂CH═CH₂ CH₂—CO₂H CH₂—CONH₂
 181. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂—CONH₂182. H OCH₂C₆H₅ CH₂—CO₂H CH₂—CONH₂
 183. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃CH₂—CONH₂
 184. H OCH₂CH₂C₆H₅ CH₂—CO₂H CH₂—CONH₂
 185. H OCH₂—CONH₂CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 186. H OCH₂—CONH₂ CH₂—CO₂H CH₂—CONH₂ 187.OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 188. OCH₂CH═CH₂ HCH₂CH₂P—O(OH)₂ CH₂—CONH₂
 189. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂190. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 191. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 192. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂CH₂—CONH₂
 193. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 194.OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 195. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂—CONH₂
 196. NH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 197. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 198. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂199. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 200. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 201. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂202. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 203. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 204. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂—CONH₂
 205. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 206. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 207. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃CH₂C₆H₅
 208. OCH₂CH═CH₂ H CH₂—CO₂H CH₂C₆H₅
 209. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃CH₂C₆H₅
 210. OCH₂C₆H₅ H CH₂—CO₂H CH₂C₆H₅
 211. OCH₂CH₂C₆H₅ HCH₂—CO₂CH₂CH₃ CH₂C₆H₅
 212. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂C₆H₅ 213.OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 214. OCH₂—CONH₂ H CH₂—CO₂H CH₂C₆H₅215. NH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 216. NH₂ H CH₂—CO₂H CH₂C₆H₅ 217.NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 218. NHSO₂CH₃ H CH₂—CO₂H CH₂C₆H₅
 219. HOCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 220. H OCH₂CH═CH₂ CH₂—CO₂H CH₂C₆H₅ 221.H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 222. H OCH₂C₆H₅ CH₂—CO₂H CH₂C₆H₅
 223. HOCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 224. H OCH₂CH₂C₆H₅ CH₂—CO₂H CH₂C₆H₅225. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 226. H OCH₂—CONH₂ CH₂—CO₂HCH₂C₆H₅
 227. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 228. OCH₂CH═CH₂ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅
 229. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅ 230.OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅
 231. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅
 232. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅
 233. OCH₂—CONH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 234. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅235. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 236. NH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅237. NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 238. NHSO₂CH₃ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅
 239. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂240. H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 241. H OCH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 242. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂243. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 244. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 245. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂246. H OCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂

TABLE IV

Ex. # X X¹ R¹ R″
 1. OCH₂CH═CH₂ H H CH₂—CO₂CH₂CH₃
 2. OCH₂CH═CH₂ H CH₃CH₂—CO₂H
 3. OCH₂C₆H₅ H H CH₂—CO₂CH₂CH₃
 4. OCH₂C₆H₅ H CH₃ CH₂—CO₂H 5.OCH₂CH₂C₆H₅ H H CH₂—CO₂CH₂CH₃
 6. OCH₂CH₂C₆H₅ H CH₃ CH₂—CO₂H 7.OCH₂—CONH₂ H H CH₂—CO₂CH₂CH₃
 8. OCH₂—CONH₂ H CH₃ CH₂—CO₂H
 9. NH₂ H HCH₂—CO₂CH₂CH₃
 10. NH₂ H CH₃ CH₂—CO₂H
 11. NHSO₂CH₃ H H CH₂—CO₂CH₂CH₃ 12.NHSO₂CH₃ H CH₃ CH₂—CO₂H
 13. H OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃
 14. HOCH₂CH═CH₂ CH₃ CH₂—CO₂H
 15. H OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃
 16. H OCH₂C₆H₅CH₃ CH₂—CO₂H
 17. H OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃
 18. H OCH₂CH₂C₆H₅ CH₃CH₂—CO₂H
 19. H OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃
 20. H OCH₂—CONH₂ CH₃ CH₂—CO₂H21. OCH₂CH═CH₂ H H CH₂CH₂—CO₂CH₂CH₃
 22. OCH₂CH═CH₂ H CH₃ CH₂CH₂—CO₂H 23.OCH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃
 24. OCH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H 25.OCH₂CH₂C₆H₅ H H CH₂CH₂—CO₂CH₂CH₃
 26. OCH₂CH₂C₆H₅ H CH₃ CH₂CH₂—CO₂H 27.OCH₂—CONH₂ H H CH₂CH₂—CO₂CH₂CH₃
 28. OCH₂—CONH₂ H CH₃ CH₂CH₂—CO₂H
 29. NH₂H H CH₂CH₂—CO₂CH₂CH₃
 30. NH₂ H CH₃ CH₂CH₂—CO₂H
 31. NHSO₂CH₃ H HCH₂CH₂—CO₂CH₂CH₃
 32. NHSO₂CH₃ H CH₃ CH₂CH₂—CO₂H
 33. H OCH₂CH═CH₂ HCH₂CH₂—CO₂CH₂CH₃
 34. H OCH₂CH═CH₂ CH₃ CH₂CH₂—CO₂H
 35. H OCH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃
 36. H OCH₂C₆H₅ CH₃ CH₂CH₂—CO₂H
 37. H OCH₂CH₂C₆H₅ HCH₂CH₂—CO₂CH₂CH₃
 38. H OCH₂CH₂C₆H₅ CH₃ CH₂CH₂—CO₂H
 39. H OCH₂—CONH₂ HCH₂CH₂—CO₂CH₂CH₃
 40. H OCH₂—CONH₂ CH₃ CH₂CH₂—CO₂H
 41. OCH₂CH═CH₂ H HCH₂CH₂P—O(OCH₂CH₃)₂
 42. OCH₂CH═CH₂ H CH₃ CH₂CH₂P—O(OH)₂
 43. OCH₂C₆H₅ H HCH₂CH₂P—O(OCH₂CH₃)₂
 44. OCH₂C₆H₅ H CH₃ CH₂CH₂P—O(OH)₂
 45. OCH₂CH₂C₆H₅ HH CH₂CH₂P—O(OCH₂CH₃)₂
 46. OCH₂CH₂C₆H₅ H CH₃ CH₂CH₂P—O(OH)₂ 47.OCH₂—CONH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂
 48. OCH₂—CONH₂ H CH₃ CH₂CH₂P—O(OH)₂49. NH₂ H H CH₂CH₂P—O(OCH₂CH₃)₂
 50. NH₂ H CH₃ CH₂CH₂P—O(OH)₂ 51.NHSO₂CH₃ H H CH₂CH₂P—O(OCH₂CH₃)₂
 52. NHSO₂CH₃ H CH₃ CH₂CH₂P—O(OH)₂
 53. HOCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂
 54. H OCH₂CH═CH₂ CH₃ CH₂CH₂P—O(OH)₂ 55.H OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂
 56. H OCH₂C₆H₅ CH₃ CH₂CH₂P—O(OH)₂
 57. HOCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂
 58. H OCH₂CH₂C₆H₅ CH₃ CH₂CH₂P—O(OH)₂59. H OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂
 60. H OCH₂—CONH₂ CH₃CH₂CH₂P—O(OH)₂
 61. OCH₂CH═CH₂ H H CH₂CH═CH—CO₂CH₂CH₃
 62. OCH₂CH═CH₂ HCH₃ CH₂CH═CH—CO₂H
 63. OCH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃
 64. OCH₂C₆H₅ H CH₃CH₂CH═CH—CO₂H
 65. OCH₂CH₂C₆H₅ H H CH₂CH═CH—CO₂CH₂CH₃
 66. OCH₂CH₂C₆H₅ HCH₃ CH₂CH═CH—CO₂H
 67. OCH₂—CONH₂ H H CH₂CH═CH—CO₂CH₂CH₃
 68. OCH₂—CONH₂ HCH₃ CH₂CH═CH—CO₂H
 69. NH₂ H H CH₂CH═CH—CO₂CH₂CH₃
 70. NH₂ H CH₃CH₂CH═CH—CO₂H
 71. NHSO₂CH₃ H H CH₂CH═CH—CO₂CH₂CH₃
 72. NHSO₂CH₃ H CH₃CH₂CH═CH—CO₂H
 73. H OCH₂CH═CH₂ H CH₂CH═CH—CO₂CH₂CH₃
 74. H OCH₂CH═CH₂ CH₃CH₂CH═CH—CO₂H
 75. H OCH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃
 76. H OCH₂C₆H₅ CH₃CH₂CH═CH—CO₂H
 77. H OCH₂CH₂C₆H₅ H CH₂CH═CH—CO₂CH₂CH₃
 78. H OCH₂CH₂C₆H₅CH₃ CH₂CH═CH—CO₂H
 79. H OCH₂—CONH₂ H CH₂CH═CH—CO₂CH₂CH₃
 80. H OCH₂—CONH₂CH₃ CH₂CH═CH—CO₂H
 81. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₃
 82. OCH₂CH═CH₂ HCH₂—CO₂H CH₃
 83. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃
 84. OCH₂C₆H₅ H CH₂—CO₂HCH₃
 85. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₃
 86. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₃87. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₃
 88. OCH₂—CONH₂ H CH₂—CO₂H CH₃
 89. NH₂H CH₂—CO₂CH₂CH₃ CH₃
 90. NH₂ H CH₂—CO₂H CH₃
 91. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃CH₃
 92. NHSO₂CH₃ H CH₂—CO₂H CH₃
 93. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₃
 94. HOCH₂CH═CH₂ CH₂—CO₂H CH₃
 95. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₃
 96. H OCH₂C₆H₅CH₂—CO₂H CH₃
 97. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₃
 98. H OCH₂CH₂C₆H₅CH₂—CO₂H CH₃
 99. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₃
 100. H OCH₂—CONH₂CH₂—CO₂H CH₃
 101. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 102. OCH₂CH═CH₂ HCH₂CH₂P—O(OH)₂ CH₃
 103. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 104. OCH₂C₆H₅H CH₂CH₂P—O(OH)₂ CH₃
 105. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₃ 106.OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₃
 107. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₃
 108. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₃
 109. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₃
 110. NH₂ H CH₂CH₂P—O(OH)₂ CH₃
 111. NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂CH₃
 112. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₃
 113. H OCH₂CH═CH₂CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 114. H OCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₃
 115. HOCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 116. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₃ 117.H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 118. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₃
 119. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₃
 120. H OCH₂—CONH₂CH₂CH₂P—O(OH)₂ CH₃
 121. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂ 122.OCH₂CH═CH₂ H CH₂—CO₂H CH₂CH═CH₂
 123. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂CH═CH₂124. OCH₂C₆H₅ H CH₂—CO₂H CH₂CH═CH₂
 125. OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃CH₂CH═CH₂
 126. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂CH═CH₂
 127. OCH₂—CONH₂ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 128. OCH₂—CONH₂ H CH₂—CO₂H CH₂CH═CH₂
 129. NH₂ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 130. NH₂ H CH₂—CO₂H CH₂CH═CH₂
 131. NHSO₂CH₃ HCH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 132. NHSO₂CH₃ H CH₂—CO₂H CH₂CH═CH₂
 133. HOCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 134. H OCH₂CH═CH₂ CH₂—CO₂H CH₂CH═CH₂135. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 136. H OCH₂C₆H₅ CH₂—CO₂HCH₂CH═CH₂
 137. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 138. H OCH₂CH₂C₆H₅CH₂—CO₂H CH₂CH═CH₂
 139. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂CH═CH₂
 140. HOCH₂—CONH₂ CH₂—CO₂H CH₂CH═CH₂
 141. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂
 142. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 143. OCH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 144. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂145. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 146. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 147. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂148. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 149. NH₂ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 150. NH₂ H CH₂CH₂P—O(OH)₂ CH₂CH═CH₂ 151.NHSO₂CH₃ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 152. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂CH₂CH═CH₂
 153. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 154. HOCH₂CH═CH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 155. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂CH₂CH═CH₂
 156. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 157. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 158. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂CH═CH₂
 159. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂CH═CH₂
 160. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂CH═CH₂
 161. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃CH₂—CONH₂
 162. OCH₂CH═CH₂ H CH₂—CO₂H CH₂—CONH₂
 163. OCH₂C₆H₅ HCH₂—CO₂CH₂CH₃ CH₂—CONH₂
 164. OCH₂C₆H₅ H CH₂—CO₂H CH₂—CONH₂ 165.OCH₂CH₂C₆H₅ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 166. OCH₂CH₂C₆H₅ H CH₂—CO₂HCH₂—CONH₂
 167. OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 168. OCH₂—CONH₂ HCH₂—CO₂H CH₂—CONH₂
 169. NH₂ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 170. NH₂ HCH₂—CO₂H CH₂—CONH₂
 171. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 172. NHSO₂CH₃H CH₂—CO₂H CH₂—CONH₂
 173. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 174. HOCH₂CH═CH₂ CH₂—CO₂H CH₂—CONH₂
 175. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂—CONH₂176. H OCH₂C₆H₅ CH₂—CO₂H CH₂—CONH₂
 177. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃CH₂—CONH₂
 178. H OCH₂CH₂C₆H₅ CH₂—CO₂H CH₂—CONH₂
 179. H OCH₂—CONH₂CH₂—CO₂CH₂CH₃ CH₂—CONH₂
 180. H OCH₂—CONH₂ CH₂—CO₂H CH₂—CONH₂ 181.OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 182. OCH₂CH═CH₂ HCH₂CH₂P—O(OH)₂ CH₂—CONH₂
 183. OCH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂184. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 185. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 186. OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OH)₂CH₂—CONH₂
 187. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂ 188.OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 189. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂—CONH₂
 190. NH₂ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 191. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 192. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂—CONH₂193. H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 194. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 195. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂196. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 197. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 198. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂—CONH₂
 199. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 200. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 201. OCH₂CH═CH₂ H CH₂—CO₂CH₂CH₃CH₂C₆H₅
 202. OCH₂CH═CH₂ H CH₂—CO₂H CH₂C₆H₅
 203. OCH₂C₆H₅ H CH₂—CO₂CH₂CH₃CH₂C₆H₅
 204. OCH₂C₆H₅ H CH₂—CO₂H CH₂C₆H₅
 205. OCH₂CH₂C₆H₅ HCH₂—CO₂CH₂CH₃ CH₂C₆H₅
 206. OCH₂CH₂C₆H₅ H CH₂—CO₂H CH₂C₆H₅ 207.OCH₂—CONH₂ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 208. OCH₂—CONH₂ H CH₂—CO₂H CH₂C₆H₅209. NHSO₂CH₃ H CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 210. NHSO₂CH₃ H CH₂—CO₂H CH₂C₆H₅211. H OCH₂CH═CH₂ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 212. H OCH₂CH═CH₂ CH₂—CO₂HCH₂C₆H₅
 213. H OCH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 214. H OCH₂C₆H₅ CH₂—CO₂HCH₂C₆H₅
 215. H OCH₂CH₂C₆H₅ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 216. H OCH₂CH₂C₆H₅CH₂—CO₂H CH₂C₆H₅
 217. H OCH₂—CONH₂ CH₂—CO₂CH₂CH₃ CH₂C₆H₅
 218. HOCH₂—CONH₂ CH₂—CO₂H CH₂C₆H₅
 219. OCH₂CH═CH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅
 220. OCH₂CH═CH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅
 221. OCH₂C₆H₅ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 222. OCH₂C₆H₅ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 223.OCH₂CH₂C₆H₅ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 224. OCH₂CH₂C₆H₅ HCH₂CH₂P—O(OH)₂ CH₂C₆H₅
 225. OCH₂—CONH₂ H CH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅226. OCH₂—CONH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅
 227. NH₂ H CH₂CH₂P—O(OCH₂CH₃)₂CH₂C₆H₅
 228. NH₂ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅
 229. NHSO₂CH₃ HCH₂CH₂P—O(OCH₂CH₃)₂ CH₂C₆H₅
 230. NHSO₂CH₃ H CH₂CH₂P—O(OH)₂ CH₂C₆H₅ 231.H OCH₂CH═CH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 232. H OCH₂CH═CH₂CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 233. H OCH₂C₆H₅ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂234. H OCH₂C₆H₅ CH₂CH₂P—O(OH)₂ CH₂—CONH₂
 235. H OCH₂CH₂C₆H₅CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 236. H OCH₂CH₂C₆H₅ CH₂CH₂P—O(OH)₂CH₂—CONH₂
 237. H OCH₂—CONH₂ CH₂CH₂P—O(OCH₂CH₃)₂ CH₂—CONH₂
 238. HOCH₂—CONH₂ CH₂CH₂P—O(OH)₂ CH₂—CONH₂

TABLE Va

Ex. # X X¹ X² X³ R¹
 1. OCH₂CO₂—CH₂CH₃ H H H H
 2. OCH₂CO₂—CH₂CH₃ H H HCH₃
 3. OCH₂CO₂H H H H H
 4. OCH₂CO₂H H H H CH₃
 5. OCH₂CH₂—CO₂CH₂CH₃ H H HH
 6. OCH₂CH₂—CO₂CH₂CH₃ H H H CH₃
 7. OCH₂CH₂—CO₂H H H H H
 8. OCH₂CH₂—CO₂HH H H CH₃
 9. OCH₂CH═CH—CO₂CH₂CH₃ H H H H
 10. OCH₂CH═CH—CO₂CH₂CH₃ H H HCH₃
 11. OCH₂CH═CH—CO₂H H H H H
 12. OCH₂CH═CH—CO₂H H H H CH₃ 13.OCH₂CH₂—PO(OCH₂CH₃)₂ H H H H
 14. OCH₂CH₂—PO(OCH₂CH₃)₂ H H H CH₃ 15.OCH₂CH₂—PO(OH)₂ H H H H
 16. OCH₂CH₂—PO(OH)₂ H H H CH₃
 17. HOCH₂CO₂—CH₂CH₃ H H H
 18. H OCH₂CO₂—CH₂CH₃ H H CH₃
 19. H OCH₂CO₂H H H H20. H OCH₂CO₂H H H CH₃
 21. H OCH₂CH₂CO₂—CH₂CH₃ H H H
 22. HOCH₂CH₂CO₂—CH₂CH₃ H H CH₃
 23. H OCH₂CH₂CO₂H H H H
 24. H OCH₂CH₂CO₂H H HCH₃
 25. H OCH₂CH═CH—CO₂CH₂CH₃ H H H
 26. H OCH₂CH═CH—CO₂CH₂CH₃ H H CH₃27. H OCH₂CH═CH—CO₂H H H H
 28. H OCH₂CH═CH—CO₂H H H CH₃
 29. HOCH₂CH₂—PO(OCH₂CH₃)₂ H H H
 30. H OCH₂CH₂—PO(OCH₂CH₃)₂ H H CH₃
 31. HOCH₂CH₂—PO(OH)₂ H H H
 32. H OCH₂CH₂—PO(OH)₂ H H CH₃
 33. H HOCH₂CO₂—CH₂CH₃ H H
 34. H H OCH₂CO₂—CH₂CH₃ H CH₃
 35. H H OCH₂CO₂H H H 36.H H OCH₂CO₂H H CH₃
 37. H H OCH₂CH₂—CO₂CH₂CH₃ H H
 38. H HOCH₂CH₂—CO₂CH₂CH₃ H CH₃
 39. H H OCH₂CH₂—CO₂H H H
 40. H H OCH₂CH₂—CO₂H HCH₃
 41. H H OCH₂—CH═CH—CO₂CH₂CH₃ H H
 42. H H OCH₂—CH═CH—CO₂CH₂CH₃ H CH₃43. H H OCH₂—CH═CHCO₂H H H
 44. H H OCH₂—CH═CHCO₂H H CH₃
 45. H HOCH₂CH₂PO—(OCH₂CH₃)₂ H H
 46. H H OCH₂CH₂PO—(OCH₂CH₃)₂ H CH₃
 47. H HOCH₂CH₂—PO(OH)₂ H H
 48. H H OCH₂CH₂—PO(OH)₂ H CH₃
 49. H H HOCH₂CO₂—CH₂CH₃ H
 50. H H H OCH₂CO₂—CH₂CH₃ CH₃
 51. H H H OCH₂CO₂H H
 52. HH H OCH₂CO₂H CH₃
 53. H H H OCH₂CH₂—CO₂CH₂CH₃ H
 54. H H HOCH₂CH₂—CO₂CH₂CH₃ CH₃
 55. H H H OCH₂CH₂—CO₂H H
 56. H H H OCH₂CH₂—CO₂HCH₃
 57. H H H OCH₂—CH═CH—CO₂CH₂CH₃ H
 58. H H H OCH₂—CH═CH—CO₂CH₂CH₃ CH₃59. H H H OCH₂—CH═CHCO₂H H
 60. H H H OCH₂—CH═CHCO₂H CH₃
 61. H H HOCH₂CH₂PO—(OCH₂CH₃)₂ H
 62. H H H OCH₂CH₂PO—(OCH₂CH₃)₂ CH₃
 63. H H HOCH₂CH₂—PO(OH)₂ H
 64. H H H OCH₂CH₂—PO(OH)₂ CH₃

TABLE Vb

Ex. # X X¹ X² X³ R¹
 1. OCH₂CO₂—CH₂CH₃ H H H H
 2. OCH₂CO₂—CH₂CH₃ H H HCH₃
 3. OCH₂CO₂H H H H H
 4. OCH₂CO₂H H H H CH₃
 5. OCH₂CH₂—CO₂CH₂CH₃ H H HH
 6. OCH₂CH₂—CO₂CH₂CH₃ H H H CH₃
 7. OCH₂CH₂—CO₂H H H H H
 8. OCH₂CH₂—CO₂HH H H CH₃
 9. OCH₂CH═CH—CO₂CH₂CH₃ H H H H
 10. OCH₂CH═CH—CO₂CH₂CH₃ H H HCH₃
 11. OCH₂CH═CH—CO₂H H H H H
 12. OCH₂CH═CH—CO₂H H H H CH₃ 13.OCH₂CH₂—PO(OCH₂CH₃)₂ H H H H
 14. OCH₂CH₂—PO(OCH₂CH₃)₂ H H H CH₃ 15.OCH₂CH₂—PO(OH)₂ H H H H
 16. OCH₂CH₂—PO(OH)₂ H H H CH₃
 17. HOCH₂CO₂—CH₂CH₃ H H H
 18. H OCH₂CO₂—CH₂CH₃ H H CH₃
 19. H OCH₂CO₂H H H H20. H OCH₂CO₂H H H CH₃
 21. H OCH₂CH₂CO₂—CH₂CH₃ H H H
 22. HOCH₂CH₂CO₂—CH₂CH₃ H H CH₃
 23. H OCH₂CH₂CO₂H H H H
 24. H OCH₂CH₂CO₂H H HCH₃
 25. H OCH₂CH═CH—CO₂CH₂CH₃ H H H
 26. H OCH₂CH═CH—CO₂CH₂CH₃ H H CH₃27. H OCH₂CH═CH—CO₂H H H H
 28. H OCH₂CH═CH—CO₂H H H CH₃
 29. HOCH₂CH₂—PO(OCH₂CH₃)₂ H H H
 30. H OCH₂CH₂—PO(OCH₂CH₃)₂ H H CH₃
 31. HOCH₂CH₂—PO(OH)₂ H H H
 32. H OCH₂CH₂—PO(OH)₂ H H CH₃
 33. H HOCH₂CO₂—CH₂CH₃ H H
 34. H H OCH₂CO₂—CH₂CH₃ H CH₃
 35. H H OCH₂CO₂H H H 36.H H OCH₂CO₂H H CH₃
 37. H H OCH₂CH₂—CO₂CH₂CH₃ H H
 38. H HOCH₂CH₂—CO₂CH₂CH₃ H CH₃
 39. H H OCH₂CH₂—CO₂H H H
 40. H H OCH₂CH₂—CO₂H HCH₃
 41. H H OCH₂—CH═CH—CO₂CH₂CH₃ H H
 42. H H OCH₂—CH═CH—CO₂CH₂CH₃ H CH₃43. H H OCH₂—CH═CHCO₂H H H
 44. H H OCH₂—CH═CHCO₂H H CH₃
 45. H HOCH₂CH₂PO—(OCH₂CH₃)₂ H H
 46. H H OCH₂CH₂PO—(OCH₂CH₃)₂ H CH₃
 47. H HOCH₂CH₂—PO(OH)₂ H H
 48. H H OCH₂CH₂—PO(OH)₂ H CH₃
 49. H H HOCH₂CO₂—CH₂CH₃ H
 50. H H H OCH₂CO₂—CH₂CH₃ CH₃
 51. H H H OCH₂CO₂H H
 52. HH H OCH₂CO₂H CH₃
 53. H H H OCH₂CH₂—CO₂CH₂CH₃ H
 54. H H HOCH₂CH₂—CO₂CH₂CH₃ CH₃
 55. H H H OCH₂CH₂—CO₂H H
 56. H H H OCH₂CH₂—CO₂HCH₃
 57. H H H OCH₂—CH═CH—CO₂CH₂CH₃ H
 58. H H H OCH₂—CH═CH—CO₂CH₂CH₃ CH₃59. H H H OCH₂—CH═CHCO₂H H
 60. H H H OCH₂—CH═CHCO₂H CH₃
 61. H H HOCH₂CH₂PO—(OCH₂CH₃)₂ H
 62. H H H OCH₂CH₂PO—(OCH₂CH₃)₂ CH₃
 63. H H HOCH₂CH₂—PO(OH)₂ H
 64. H H H OCH₂CH₂—PO(OH)₂ CH₃

TABLE VIIa

Ex. # X X¹ X² R
 1. OCH₂CH═CH₂ H H H
 2. OCH₂CH═CH₂ H H CH₃
 3. NHSO₂CH₃ HH H
 4. NHSO₂CH₃ H H CH₃
 5. OCH₂C₆H₅ H H H
 6. OCH₂C₆H₅ H H CH₃ 7.OCH₂C₆H₄—Cl(3) H H H
 8. OCH₂C₆H₄—Cl(3) H H CH₃
 9. OCH₂C₆H₄—Cl(4) H H H10. OCH₂C₆H₄—Cl(4) H H CH₃
 11. OCH₂C₆H₄—F(3) H H H
 12. OCH₂C₆H₄—F(3) H HCH₃
 13. OCH₂C₆H₄—F(4) H H H
 14. OCH₂C₆H₄—F(4) H H CH₃ 15.OCH₂C₆H₄—CF₃(3) H H H
 16. OCH₂C₆H₄—CF₃(3) H H CH₃
 17. OCH₂C₆H₄—CF₃(4) HH H
 18. OCH₂C₆H₄—CF₃(4) H H CH₃
 19. OCH₂C₆H₄—NO₂(3) H H H 20.OCH₂C₆H₄—NO₂(3) H H CH₃
 21. OCH₂C₆H₄—NO₂(4) H H H
 22. OCH₂C₆H₄—NO₂(4) HH CH₃
 23. OCH₂C₆H₄—NHSO₂CH₃(3) H H H
 24. OCH₂C₆H₄—NHSO₂CH₃(3) H H CH₃25. OCH₂C₆H₄—NHSO₂CH₃(4) H H H
 26. OCH₂C₆H₄—NHSO₂CH₃(4) H H CH₃ 27.OCH₂C₆H₄—CN(3) H H H
 28. OCH₂C₆H₄—CN(3) H H CH₃
 29. OCH₂C₆H₄—CN(4) H H H30. OCH₂C₆H₄—CN(4) H H CH₃
 31. OCH₂C₆H₄—CONH₂(3) H H H 32.OCH₂C₆H₄—CONH₂(3) H H CH₃
 33. OCH₂C₆H₄—CONH₂(4) H H H 34.OCH₂C₆H₄—CONH₂(4) H H CH₃
 35. OCH₂C₆H₄—CH₂CN(3) H H H 36.OCH₂C₆H₄—CH₂CN(3) H H CH₃
 37. OCH₂C₆H₄—CH₂CN(4) H H H 38.OCH₂C₆H₄—CH₂CN(4) H H CH₃
 39. OCH₂C₆H₄—CH₂CONH₂(3) H H H 40.OCH₂C₆H₄—CH₂CONH₂(3) H H CH₃
 41. OCH₂C₆H₄—CH₂CONH₂(4) H H H 42.OCH₂C₆H₄—CH₂CONH₂(4) H H CH₃
 43. OCH₂C₆H₄—OCH₂CN(3) H H H 44.OCH₂C₆H₄—OCH₂CN(3) H H CH₃
 45. OCH₂C₆H₄—OCH₂CN(4) H H H 46.OCH₂C₆H₄—OCH₂CN(4) H H CH₃
 47. OCH₂C₆H₄—OCH₂CONH₂(3) H H H 48.OCH₂C₆H₄—OCH₂CONH₂(3) H H CH₃
 49. OCH₂C₆H₄—OCH₂CONH₂(4) H H H 50.OCH₂C₆H₄—OCH₂CONH₂(4) H H CH₃
 51. OCH₂C₆H₃—(CN)₂(3,5) H H H 52.OCH₂C₆H₃—(CN)₂(3,5) H H CH₃
 53. OCH₂C₆H₃—(CN)₂(3,5) H H H 54.OCH₂C₆H₃—(CN)₂(3,5) H H CH₃
 55. OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 56.OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃
 57. OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 58.OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃
 59. OCH₂CH₂C₆H₅ H H H
 60. OCH₂CH₂C₆H₅ H HCH₃
 61. OCH₂C₆H₄C₆H₄CN(2) H H H
 62. OCH₂C₆H₄C₆H₄CN(2) H H CH₃ 63.OCH₂C₆H₄C₆H₄CONH₂(2) H H H
 64. OCH₂C₆H₄C₆H₄CONH₂(2) H H CH₃

TABLE VIIb

Ex. # X¹ X X² R
 1. OCH₂CH═CH₂ H H H
 2. OCH₂CH═CH₂ H H CH₃
 3. NHSO₂CH₃ HH H
 4. NHSO₂CH₃ H H CH₃
 5. OCH₂C₆H₅ H H H
 6. OCH₂C₆H₅ H H CH₃ 7.OCH₂C₆H₄—Cl(3) H H H
 8. OCH₂C₆H₄—Cl(3) H H CH₃
 9. OCH₂C₆H₄—Cl(4) H H H10. OCH₂C₆H₄—Cl(4) H H CH₃
 11. OCH₂C₆H₄—F(3) H H H
 12. OCH₂C₆H₄—F(3) H HCH₃
 13. OCH₂C₆H₄—F(4) H H H
 14. OCH₂C₆H₄—F(4) H H CH₃ 15.OCH₂C₆H₄—CF₃(3) H H H
 16. OCH₂C₆H₄—CF₃(3) H H CH₃
 17. OCH₂C₆H₄—CF₃(4) HH H
 18. OCH₂C₆H₄—CF₃(4) H H CH₃
 19. OCH₂C₆H₄—NO₂(3) H H H 20.OCH₂C₆H₄—NO₂(3) H H CH₃
 21. OCH₂C₆H₄—NO₂(4) H H H
 22. OCH₂C₆H₄—NO₂(4) HH CH₃
 23. OCH₂C₆H₄—NHSO₂CH₃(3) H H H
 24. OCH₂C₆H₄—NHSO₂CH₃(3) H H CH₃25. OCH₂C₆H₄—NHSO₂CH₃(4) H H H
 26. OCH₂C₆H₄—NHSO₂CH₃(4) H H CH₃ 27.OCH₂C₆H₄—CN(3) H H H
 28. OCH₂C₆H₄—CN(3) H H CH₃
 29. OCH₂C₆H₄—CN(4) H H H30. OCH₂C₆H₄—CN(4) H H CH₃
 31. OCH₂C₆H₄—CONH₂(3) H H H 32.OCH₂C₆H₄—CONH₂(3) H H CH₃
 33. OCH₂C₆H₄—CONH₂(4) H H H 34.OCH₂C₆H₄—CONH₂(4) H H CH₃
 35. OCH₂C₆H₄—CH₂CN(3) H H H 36.OCH₂C₆H₄—CH₂CN(3) H H CH₃
 37. OCH₂C₆H₄—CH₂CN(4) H H H 38.OCH₂C₆H₄—CH₂CN(4) H H CH₃
 39. OCH₂C₆H₄—CH₂CONH₂(3) H H H 40.OCH₂C₆H₄—CH₂CONH₂(3) H H CH₃
 41. OCH₂C₆H₄—CH₂CONH₂(4) H H H 42.OCH₂C₆H₄—CH₂CONH₂(4) H H CH₃
 43. OCH₂C₆H₄—OCH₂CN(3) H H H 44.OCH₂C₆H₄—OCH₂CN(3) H H CH₃
 45. OCH₂C₆H₄—OCH₂CN(4) H H H 46.OCH₂C₆H₄—OCH₂CN(4) H H CH₃
 47. OCH₂C₆H₄—OCH₂CONH₂(3) H H H 48.OCH₂C₆H₄—OCH₂CONH₂(3) H H CH₃
 49. OCH₂C₆H₄—OCH₂CONH₂(4) H H H 50.OCH₂C₆H₄—OCH₂CONH₂(4) H H CH₃
 51. OCH₂C₆H₃—(CN)₂(3,5) H H H 52.OCH₂C₆H₃—(CN)₂(3,5) H H CH₃
 53. OCH₂C₆H₃—(CN)₂(3,5) H H H 54.OCH₂C₆H₃—(CN)₂(3,5) H H CH₃
 55. OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 56.OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃
 57. OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 58.OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃
 59. OCH₂CH₂C₆H₅ H H H
 60. OCH₂CH₂C₆H₅ H HCH₃
 61. OCH₂C₆H₄C₆H₄CN(2) H H H
 62. OCH₂C₆H₄C₆H₄CN(2) H H CH₃ 63.OCH₂C₆H₄C₆H₄CONH₂(2) H H H
 64. OCH₂C₆H₄C₆H₄CONH₂(2) H H CH₃

TABLE VIIc

Ex. # X² X X¹ R
 1. OCH₂CH═CH₂ H H H
 2. OCH₂CH═CH₂ H H CH₃
 3. NHSO₂CH₃ HH H
 4. NHSO₂CH₃ H H CH₃
 5. OCH₂C₆H₅ H H H
 6. OCH₂C₆H₅ H H CH₃ 7.OCH₂C₆H₄—Cl(3) H H H
 8. OCH₂C₆H₄—Cl(3) H H CH₃
 9. OCH₂C₆H₄—Cl(4) H H H10. OCH₂C₆H₄—Cl(4) H H CH₃
 11. OCH₂C₆H₄—F(3) H H H
 12. OCH₂C₆H₄—F(3) H HCH₃
 13. OCH₂C₆H₄—F(4) H H H
 14. OCH₂C₆H₄—F(4) H H CH₃ 15.OCH₂C₆H₄—CF₃(3) H H H
 16. OCH₂C₆H₄—CF₃(3) H H CH₃
 17. OCH₂C₆H₄—CF₃(4) HH H
 18. OCH₂C₆H₄—CF₃(4) H H CH₃
 19. OCH₂C₆H₄—NO₂(3) H H H 20.OCH₂C₆H₄—NO₂(3) H H CH₃
 21. OCH₂C₆H₄—NO₂(4) H H H
 22. OCH₂C₆H₄—NO₂(4) HH CH₃
 23. OCH₂C₆H₄—NHSO₂CH₃(3) H H H
 24. OCH₂C₆H₄—NHSO₂CH₃(3) H H CH₃25. OCH₂C₆H₄—NHSO₂CH₃(4) H H H
 26. OCH₂C₆H₄—NHSO₂CH₃(4) H H CH₃ 27.OCH₂C₆H₄—CN(3) H H H
 28. OCH₂C₆H₄—CN(3) H H CH₃
 29. OCH₂C₆H₄—CN(4) H H H30. OCH₂C₆H₄—CN(4) H H CH₃
 31. OCH₂C₆H₄—CONH₂(3) H H H 32.OCH₂C₆H₄—CONH₂(3) H H CH₃
 33. OCH₂C₆H₄—CONH₂(4) H H H 34.OCH₂C₆H₄—CONH₂(4) H H CH₃
 35. OCH₂C₆H₄—CH₂CN(3) H H H 36.OCH₂C₆H₄—CH₂CN(3) H H CH₃
 37. OCH₂C₆H₄—CH₂CN(4) H H H 38.OCH₂C₆H₄—CH₂CN(4) H H CH₃
 39. OCH₂C₆H₄—CH₂CONH₂(3) H H H 40.OCH₂C₆H₄—CH₂CONH₂(3) H H CH₃
 41. OCH₂C₆H₄—CH₂CONH₂(4) H H H 42.OCH₂C₆H₄—CH₂CONH₂(4) H H CH₃
 43. OCH₂C₆H₄—OCH₂CN(3) H H H 44.OCH₂C₆H₄—OCH₂CN(3) H H CH₃
 45. OCH₂C₆H₄—OCH₂CN(4) H H H 46.OCH₂C₆H₄—OCH₂CN(4) H H CH₃
 47. OCH₂C₆H₄—OCH₂CONH₂(3) H H H 48.OCH₂C₆H₄—OCH₂CONH₂(3) H H CH₃
 49. OCH₂C₆H₄—OCH₂CONH₂(4) H H H 50.OCH₂C₆H₄—OCH₂CONH₂(4) H H CH₃
 51. OCH₂C₆H₃—(CN)₂(3,5) H H H 52.OCH₂C₆H₃—(CN)₂(3,5) H H CH₃
 53. OCH₂C₆H₃—(CN)₂(3,5) H H H 54.OCH₂C₆H₃—(CN)₂(3,5) H H CH₃
 55. OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 56.OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃
 57. OCH₂C₆H₃—(CONH₂)₂(3,5) H H H 58.OCH₂C₆H₃—(CONH₂)₂(3,5) H H CH₃
 59. OCH₂CH₂C₆H₅ H H H
 60. OCH₂CH₂C₆H₅ H HCH₃
 61. OCH₂C₆H₄C₆H₄CN(2) H H H
 62. OCH₂C₆H₄C₆H₄CN(2) H H CH₃ 63.OCH₂C₆H₄C₆H₄CONH₂(2) H H H
 64. OCH₂C₆H₄C₆H₄CONH₂(2) H H CH₃